朊蛋白基因表达与传染性海绵状脑病发生发展关系的研究
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摘要
传染性海绵状脑病是一组人类和动物的神经退行性疾病,人们认为该病是由机体正常编码的朊蛋白基因表达的细胞型朊蛋白(PrP~C)转变为蛋白酶抗性的致病性朊蛋白(PrP~(SC))而导致。在疾病发生、发展过程中,PrP~(SC)作为模板诱导基础分子PrP~C发生构象的改变,导致PrP~C形成PrP~(SC)并在中枢神经系统聚集,引发动物的传染性海绵状脑病。因此,研究作为基础分子的细胞型朊蛋白的表达及其在TSE病理发生中的作用是研究动物传染性海绵状脑病的关键点,对探索动物传染性海绵状脑病的发生、发展具有重要的意义。目前,动物传染性海绵状脑病的研究主要依赖于实验动物和培养神经细胞两种模型。本研究针对这两种模型,从朊蛋白基因表达及其参与TSE发生、发展的角度,对野生型金黄地鼠中枢神经和外周组织朊蛋白基因的表达模式、发育相关的动态表达、处理重组朊蛋白脑内接种的影响和细胞型朊蛋白在培养SD大鼠神经源性细胞作用模型病理发生中的作用等方面进行了剖析,为探索动物传染性海绵状脑病发生的分子机理和朊蛋白与疾病发生、发展的关系提供了基础数据,研究内容如下:
1 为探索实验动物朊蛋白基因的表达模式和发育相关的动态表达,对不同年龄段的野生型金黄地鼠进行了中枢神经系统和外周器官朊蛋白基因表达的定量。结果显示:同一年龄点,朊蛋白基因在脑内各部位和淋巴系统内的表达量显著高于外周器官;随着年龄的变化,朊蛋白基因的表达呈现特定的时间相关性变化。朊蛋白基因表达的组织特异性和时间相关的动态变化将揭示朊蛋白与疾病发生的关系。
2 对重组牛朊蛋白进行了化学处理后脑内接种金黄地鼠,200天后对朊蛋白抗性进行了western-blotting检测,对脑组织朊蛋白基因的表达进行了分析。结果发现实验组和对照组朊蛋白基因表达无显著差异;对实验组和对照组脑部3个部位的westem-Blot检测发现蛋白量也无显著差异;采用蛋白酶消化后,无抗性蛋白出现。
3 利用物理和酶消化相结合的分离方法,结合药物选择和差速粘附等纯化手段,成功地对野生型SD大鼠大脑皮质神经元、大脑皮质星形胶质细胞和小脑颗粒神经元进行了体外的分离、培养和鉴定。为研究动物传染性海绵状脑病致病机理细胞模型的建立提供了良好的实验材料。
4 为研究动物传染性海绵状脑病中神经元退行性病变和胶质细胞增生的机理,按照体外模拟的原则,利用人工合成的PrP~(SC)类似物构建野生型SD大鼠神经源性细胞模型,对神经元和胶质细胞的存活率及基因相对表达进行了研究。结果发现,朊蛋白多肽在50μM浓度下,在间期作用时,可以引起大脑皮质神经元和小脑颗粒神经元的显著死亡,而胶质细胞增生明显。在此作用模型下,神经细胞的朊蛋白基因表达在特定的时间出现显著的下降,而星形胶质细胞朊蛋白的基因表达显著上升。结果提示,朊蛋白通过调节其基因的表达水平而对神经元产生毒性作用。
Transmissible spongiform encephalopathies (TSE) are a group of fatal neurodegenerative disorders of animals and humans, it is widely accepted that the conformational conversion of host-coded PrP~C into a relatively protease-resistant isoform PrP~SC (disease-associated form) which is the Pathogenesis of TSE. PtP~C serving as a substrate molecule and PrP~SC acting as a template in the development of the disease induce PrP~C conversion to PrP~SC; then the aggregation of PrP~SC in the central nervous system result in TSE. It is defining event to study the expression of PrP gene serving as a substrate molecule and has important sense to explore the mechanism of TSE. Now researches on the mechanism rely on the model of experimental animals and cultured neuronal cells. With the points of prion gene expression and its impaction on the development of TSE, we analyzed the prion gene expression of tissues of wild-type golden hamster, the animal model that golden hamster injected in brain by treated purified prion recombinant structure protein and the cultured neuronal cell model originate from SD rat. What we got will provide the foundational data for the mechanism of TSE and the function of prion protein. The content is as follows:1. The present work determined prion gene expression in CNS and peripheral tissues of normal golden hamster of varies ages to explor the expression model of the experimental animal. CNS tissues sampled included neocortex, cerebellum, thalamus and obex. Peripheral organs sampled included spleen and inguinal shallow lymph nodes with respect to lymphoid organs and heart, liver, kidney and lung. The results showed that the gene expression is higher in CNS tissues than that in peripheral organs and pertinent to ages. Tissue specific prion gene expression and dynamic variability is consistent with the function of prion protein in occurrence of TSE.2. Recombinant bovine prion protein was treated by chemical solution, and the treated Recombinant bovine prion protein was intracerebrally inoculated in the brain. The prion gene expression was quantified and the proteinase resistant protein was detected by western-blotting. The results showed that there was no difference between the experimental group and the control in prion gene expression and there also no difference in protein level at three detected sites in brain. Using the proteinase K to digest, there was no resistant protein occurred.3. Using the combination of physical and enzyme digested separate techniques and utilizing medication or different adhesion rates, cerebral neuron cells, astrocytes and cerebella granule neuronal cells were successfully separated, cultured and identified. All that provided the favorable experimental materials for research on mechanism of transmissible spongiform encephalopathies.4. To study the mechanism of neuronal degeneration and gliosis in transmissible spongiform encephalopathies, we constructed the cultured neuronal cells and astrocytes cells model by PrP~SC like prion protein peptide based on the proper principia. Quantification of the prion gene
expression and cells livabilities were studied for the cultured neuronal cells model. The results showed that the cultured cerebral neuron cells and cerebellar granule neurons had significant death that treated by the prion protein peptide at 50μM concentration while the cerebral astrocytes exhibited hyperplasia under the same circumstance. Under the same treatment regimens, the level of PrP gene expression was significantly down-regulated in cortical neuron cell cultures and cerebellar granule cell cultures and was up-regulated in astrocyte cultures. These findings indicate that PrP peptide regulates transcription of the PrP gene and this activity is associated with its neurotoxicity in primary rat neuronal cultures and the similar processes happened with the occurrence of the Transmissible spongiform encephalopathies.
1 为探索实验动物朊蛋白基因的表达模式和发育相关的动态表达,对不同年龄段的野生型金黄地鼠进行了中枢神经系统和外周器官朊蛋白基因表达的定量。结果显示:同一年龄点,朊蛋白基因在脑内各部位和淋巴系统内的表达量显著高于外周器官;随着年龄的变化,朊蛋白基因的表达呈现特定的时间相关性变化。朊蛋白基因表达的组织特异性和时间相关的动态变化将揭示朊蛋白与疾病发生的关系。
2 对重组牛朊蛋白进行了化学处理后脑内接种金黄地鼠,200天后对朊蛋白抗性进行了western-blotting检测,对脑组织朊蛋白基因的表达进行了分析。结果发现实验组和对照组朊蛋白基因表达无显著差异;对实验组和对照组脑部3个部位的westem-Blot检测发现蛋白量也无显著差异;采用蛋白酶消化后,无抗性蛋白出现。
3 利用物理和酶消化相结合的分离方法,结合药物选择和差速粘附等纯化手段,成功地对野生型SD大鼠大脑皮质神经元、大脑皮质星形胶质细胞和小脑颗粒神经元进行了体外的分离、培养和鉴定。为研究动物传染性海绵状脑病致病机理细胞模型的建立提供了良好的实验材料。
4 为研究动物传染性海绵状脑病中神经元退行性病变和胶质细胞增生的机理,按照体外模拟的原则,利用人工合成的PrP~(SC)类似物构建野生型SD大鼠神经源性细胞模型,对神经元和胶质细胞的存活率及基因相对表达进行了研究。结果发现,朊蛋白多肽在50μM浓度下,在间期作用时,可以引起大脑皮质神经元和小脑颗粒神经元的显著死亡,而胶质细胞增生明显。在此作用模型下,神经细胞的朊蛋白基因表达在特定的时间出现显著的下降,而星形胶质细胞朊蛋白的基因表达显著上升。结果提示,朊蛋白通过调节其基因的表达水平而对神经元产生毒性作用。
Transmissible spongiform encephalopathies (TSE) are a group of fatal neurodegenerative disorders of animals and humans, it is widely accepted that the conformational conversion of host-coded PrP~C into a relatively protease-resistant isoform PrP~SC (disease-associated form) which is the Pathogenesis of TSE. PtP~C serving as a substrate molecule and PrP~SC acting as a template in the development of the disease induce PrP~C conversion to PrP~SC; then the aggregation of PrP~SC in the central nervous system result in TSE. It is defining event to study the expression of PrP gene serving as a substrate molecule and has important sense to explore the mechanism of TSE. Now researches on the mechanism rely on the model of experimental animals and cultured neuronal cells. With the points of prion gene expression and its impaction on the development of TSE, we analyzed the prion gene expression of tissues of wild-type golden hamster, the animal model that golden hamster injected in brain by treated purified prion recombinant structure protein and the cultured neuronal cell model originate from SD rat. What we got will provide the foundational data for the mechanism of TSE and the function of prion protein. The content is as follows:1. The present work determined prion gene expression in CNS and peripheral tissues of normal golden hamster of varies ages to explor the expression model of the experimental animal. CNS tissues sampled included neocortex, cerebellum, thalamus and obex. Peripheral organs sampled included spleen and inguinal shallow lymph nodes with respect to lymphoid organs and heart, liver, kidney and lung. The results showed that the gene expression is higher in CNS tissues than that in peripheral organs and pertinent to ages. Tissue specific prion gene expression and dynamic variability is consistent with the function of prion protein in occurrence of TSE.2. Recombinant bovine prion protein was treated by chemical solution, and the treated Recombinant bovine prion protein was intracerebrally inoculated in the brain. The prion gene expression was quantified and the proteinase resistant protein was detected by western-blotting. The results showed that there was no difference between the experimental group and the control in prion gene expression and there also no difference in protein level at three detected sites in brain. Using the proteinase K to digest, there was no resistant protein occurred.3. Using the combination of physical and enzyme digested separate techniques and utilizing medication or different adhesion rates, cerebral neuron cells, astrocytes and cerebella granule neuronal cells were successfully separated, cultured and identified. All that provided the favorable experimental materials for research on mechanism of transmissible spongiform encephalopathies.4. To study the mechanism of neuronal degeneration and gliosis in transmissible spongiform encephalopathies, we constructed the cultured neuronal cells and astrocytes cells model by PrP~SC like prion protein peptide based on the proper principia. Quantification of the prion gene
expression and cells livabilities were studied for the cultured neuronal cells model. The results showed that the cultured cerebral neuron cells and cerebellar granule neurons had significant death that treated by the prion protein peptide at 50μM concentration while the cerebral astrocytes exhibited hyperplasia under the same circumstance. Under the same treatment regimens, the level of PrP gene expression was significantly down-regulated in cortical neuron cell cultures and cerebellar granule cell cultures and was up-regulated in astrocyte cultures. These findings indicate that PrP peptide regulates transcription of the PrP gene and this activity is associated with its neurotoxicity in primary rat neuronal cultures and the similar processes happened with the occurrence of the Transmissible spongiform encephalopathies.
引文
[1] Liemann S, Glockshuber R. Transmissible spongiform encephalopathies. Biochem Biophys Res Commun, 1998, 250: 187-190
[2] Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science, 1982, 216: 136-144
[3] Chiarini LB, Freitas AR, Zanata SM, Brentani RR, Martins VR, Linden R. Cellular prion protein transduces neuroprotective signals. EMBO J, 2002, 21, 3317-3326
[4] Zou WQ, Zheng J, Gray DM, Gambetti P, Chen SG. Antibody to DNA detects scrapie but not normal priori protein. Proc Natl Acad Sci USA, 2004, 101: 1380-1385
[5] Adler V, Zeiler B, Kryukov V, Kascsak R, Rubenstein R, Grossman A. Small, highly structured RNAs participate in the conversion of human recombinant PrPsen to PrPres in vitro. J Mol Biol, 2003, 332: 47-57
[6] McBride PA, Eikelenboom P, Kraal G, Fraser H, Bruce ME. PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. J Pathol, 1992, 168(4): 413-418
[7] Humphrey JH, Grennan D, Sundaram V. The origin of follicular dendritic cells in the mouse and the mechanism of trapping of immune complexes on them. Eur J Immunol, 1984, 14(9): 859-864
[8] Montrasio F, Cozzio A, Flechsig E, Rossi D, Klein MA, Rulicke T, Raeber A J, Vosshenrich CA, Proft J, Aguzzi A, Weissmann C. B lymphocyte-restricted expression of prion protein does not enable prion replication in priori protein knockout mice. Proc Natl Acad Sci U S A, 2001, 98 (7): 4034-4037
[9] Bencsik A, Lezmi S, Hunsmann G, Baron T. Close vicinity of PrP expressing cells (FDC) with noradrenergic fibers in healthy sheep spleen. Dev Immunol, 2001, 8(3-4): 235-241
[10] Glatzel M, Giger O, Braun N, Aguzzi A. The peripheral nervous system and the pathogenesis of prion diseases. Curr Mol Med, 2004, 4(4): 355-359
[11] Beekes M, McBride PA. Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie. Neurosci Lett, 2000, 278(3): 181-184
[12] Houston F, Foster JD, Chong A, Hunter N, Bostock CJ. Transmission of BSE by blood transfusion in sheep. Lancet, 2000, 356(9234): 999-1000
[13] Fischer MB, Roeckl C, Parizek P, Schwarz HP, Aguzzi A. Binding of disease-associated prion protein to plasminogen. Nature, 2000, 408(6811): 479-483
[14] Singh N, Gu Y, Bose S, Kalepu S, Mishra RS, Verghese S. Prion peptide 106-126 as a model for prion replication and neurotoxicity. Front Biosci, 2002, 7: 60-71
[15] Ciesielski-Treska J, Grant NJ, Ulrich G, Corrotte M, Bailly Y, Haeberle AM, Chasserot-Golaz S, Bader MF. Fibrillar prion peptide (106-126) and scrapie prion protein hamper phagocytosis in microglia. Glia, 2004, 46(2): 101-115
[16] Kaneider NC, Kaser A, Dunzendorfer S, Tilg H, Patsch JR, Wiedermann CJ. Neurokinin-l receptor interacts with PrP (106-126)-induced dendritic cell migration and maturation. J Neuroimmunol, 2005, 158(1-2): 153-158
[17] Haik S, Peyrin JM, Lins L, Rosseneu MY, Brasseur R, Langeveld JP, Tagliavini F, Deslys JP, Lasmezas C, Dormont D. Neurotoxicity of the putative transmembrane domain of the prion protein. Neurobiol Dis, 2000, 7: 644-656
[18] Fabrizi C, Silei V, Menegazzi M, Salmona M, Bugiani O, Tagliavini F, Suzuki H, Lauro GM. The stimulation of inducible nitric-oxide synthase by the priori protein fragment 106—126 in human microglia is tumor necrosis factor-alpha-dependent and involves p38 mitogen-activated protein kinase. J Biol Chem, 2001, 276(28): 25692-25696
[19] Kourie JI. Mechanisms of prion-induced modifications in membrane transport properties: implications for signal transduction and neurotoxicity. Chem Biol Interact, 2001, 138(1): 1-26
[20] Requena JR, Dimitrova MN, Legname G, Teijeira S, Prusiner SB, Levine RL. Oxidation of methionine residues in the prion protein by hydrogen peroxide. Arch Biochem Biophys, 2004, 432(2): 188-195
[21] Kourie JI, Farrelly PV, Henry CL. Channel activity of deamidated isoforms of prion protein fragment 106-126 in planar lipid bilayers. J Neurosci Res, 2001, 66(2): 214-220
[22] Agostinho P, Oliveira CR. Involvement of calcineurin in the neurotoxic effects induced by amyloid-beta and prion peptides. Eur J Neurosci, 2003, 17(6): 1189-1196
[23] Roucou X, Gains M, LeBlanc AC. Neuroprotective functions of priori protein. J Neurosci Res, 2004, 75: 153-161
[24] Wong BS, Pan T, Liu T, Li R, Petersen RB, Jones IM, Gambetti P, Brown DR, Sy MS. Prion disease: a loss of antioxidant function? Biochem Biophys Res Commun, 2000, 275: 249-252
[25] Caughey B, Raymond G J, Callahan MA, et al. Interactions and conversions of prion protein isoforms. Adv Protein Chem, 2001, 57: 139-169
[26] Hadlow W J. Scrapie and kuru. Lancet, 1959, 2: 289-290
[27] Chandler R L. Encephalopathy in mice produced by inoculation with scrapie brain material. Lance, 1961, 1: 1378-1379
[28] Alper T, Haig DA, Clarke MC. The exceptionally small size of the scrapie agent. Biochemistry and Biophysics Research Communications, 1966, 22: 278-284
[29] Alper T, Cramp WA, Haig DA, Clarke MC. Does the agent of scrapie replicate without nucleic acid? Nature, 1967, 214: 764-766
[30] Dickinson AG, Outram GW. The scrapie replication-site hypothesis and its implications for pathogenesis. In: PRUSINER SB & HADLOW WJ, (Eds). Slow transmissible diseases of the nervous system. Academic Press, New York, 1979, 2: 13-31
[31] Besnoit MM, Morel Ch. Note sur les lesions nerveuses de la tremblante du mouton. Revue Vet Prinaire, 1998, ⅹⅹⅢ (LV), 27-400
[32] Aucouturier P, Carp RI, Carnaud C, Wisniewski T. Prion diseases and the immune system. Clin Immunol, 2000, 96: 79-85
[33] Cashman NR, Loertscher R, Nalbantoglu J, Shaw I, Kascsak RJ, Bolton DC, Bendheim PE. Cellular isoform of the scrapie agent protein participates in lymphocyte activation. Cell, 1990, 61: 185-92
[34] Hope J, Shearman M S, Baxter H C, et al. Cytotoxicity of prion protein peptide (PrP106-126) differs in mechanism from the cytotoxic activity of the Alzheimer's disease amyloid peptide, A beta 25-35. Neurodegeneration, 1996, 5(1): 1-11
[35] Kawahara M, Kuroda Y, Arispe N, et al. Alzheimer's beta-amyloid, human islet amylin, and prion protein fragment evoke intracellular free calcium elevations by a common mechanism in a hypothalamic GnRH neuronal cell line. J Biol Chem, 2000, 275(19): 14077-14083
[36] Mouillet-Richard S, Ermonval M, Chebassier C, Laplanche JL, Lehmann S, Launay JM, Kellermann O. Signal transduction through prion protein. Science, 2000, 289: 1925-1928
[37] Brown D R. Role of the prion protein in copper turnover in astrocytes. Neurobiol Dis, 2004, 15(3): 534-543
[38] Glatzel M, Aguzzi A. PrP(C) expression in the peripheral nervous system is a determinant of prion neuroinvasion. J Gen Virol, 2000, 81: 2813-2821
[39] Zanusso G, Liu D, Ferrari S, Hegyi I, Yin X, Aguzzi A, Hornemann S, Liemann S, Glockshuber R, Manson JC. Prion proteinexpression in different species: analysis with a panel of new mAbs. Proc Natl Acad Sci USA, 1998, 5: 8812-8816
[40] Robakis NK, Sawh PR, Wolfe GC, Rubenstein R, Carp RI, Irmis MA. Isolation of a cDNA clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues. Proc Natl Acad Sci USA, 1986, 83: 6377-6381
[41] Harris DA, Lele P, Snider WD. Localization of the mRNA for a chicken prion protein by in situ hybridization. Proc Natl Acad Sci USA, 1993, 90: 4309-4313
[42] Harris DA, Falls DL, Johnson FA, Fischbach GD. A prion-like protein from chicken brain copurifies with an acetylcholine receptor-inducing activity. Proc Natl Acad Sci USA, 1991, 88:7664-7668
[43] Ford MJ, Burton LJ, Morris RJ, Hall SM. Selective expression of prion protein peripheral tissues of the adult mouse. Neuroscience, 2002, 113(1): 177-192
[44] Tichopad A, Pfaffl MW, Didier A. Tissue-specific expression pattern of bovine prion gene: quantification using real-time RT-PCR. Molecular and Cellular Probes, 2003, 17: 5-10
[45] Selvaggini C, De Gioia L, Cantu L, Ghibaudi E, Diomede L, Passerini F, Forloni G, Bugiani O, Tagliavini F, Salmona M. Molecular characteristics of a protease-resistant, amyloidogenic and neurotoxic peptide homologous to residues 106-126 of the prion protein. Biochem Biophys Res Commun, 1993, 194(3): 1380-1386.
[46] Gu Y, Fujioka H, Mishra R S, et al. Prion peptide 106-126 modulates the aggregation of cellular prion protein and induces the synthesis of potentially neurotoxic transmembrane PrP. J Biol Chem. 2002, 277: 2275-2286.
[47] Stewart RS, Drisaldi B, Harris DA. A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic Reticulum. Mol Biol Cell, 2001, 12(4): 881-889
[48] Pan T, Li R, Wong BS, Liu T, Gambetti P, Sy MS. Heterogeneity of normal prion protein in twodimensional immunoblot: presence of various glycosylated and truncated forms. J Neurochem, 2002, 81(5): 1092-101
[49] Caughey B, Neary K, Buller R, Ernst D, Perry LL, Chesebro B, Race RE. Normal and scrapieassociated forms of prion protein differ in their sensitivities to phospholipase and proteases in intact neuroblastoma cells. J Virol, 1990, 64(3): 1093-101.
[50] Borchelt DR, Lee MK, Slunt HS, Guarnieri M, Xu ZS, Wong PC, Brown RH Jr, Price DL, Sisodia SS, Cleveland DW. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc Natl Acad Sci US A, 1994, 91 (17): 8292-6.
[51] Sabuncu E, Petit S, Le Dur A, Lan Lai T, Vilotte JL, Laude H, Vilette DPrP polymorphisms tightly control sheep prion replication in cultured cells. J Virol, 2003, 77 (4): 2696-700.
[52] Brown DR. Prion and prejudice: normal protein at the synapse. Trends Neurosci, 2001, 24: 85-90[53] Brown DR. Copper and prion disease Brain Res Bull, 2001, 55: 165-173
[54] Bouzamondo-Bemstein E, Hopkins SD, Spilman P, Uyehara-Lock J, Deering C, Safar J, Prusiner SB, Ralston HJ 3rd, DeArmond SJ. The neurodegeneration sequence in prion diseases: evidence from functional, morphological and ultrastructural studies of the GABA ergic system. J Neuropathol Exp Neurol, 2004, 63(8): 882-99.
[55] Collinge J, Whittington MA, Sidle KC, Smith CJ, Palmer MS, Clarke AR, Jefferys JG. Prion protein is necessary for normal synaptic function. Nature, 1994, 370(6487): 295-7.
[56] Karmenberg K, Groschup MH, Sigel E. Cellular prion protein and GABAA receptors: no physical association? Neuroreport, 1995, 7(1): 77-80.
[57] Lu P, Sturman JA, Bolton DC. Altered GABA distribution in hamster brain is an early molecular consequence of infection by scrapie prions. Brain Res, 1995, 681(1-2): 235-41.
[58] Sakaguchi S, Katamine S, Nishida N, Moriuchi R, Shigematsu K, Sugimoto T, Nakatani A, Kataoka Y, Houtani T, Shirabe S, Okada H, Hasegawa S, Miyamoto T, Noda T. Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene. Nature, 1996, 380(6574): 528-531.
[59] Brown DR. An alternative cause for BSE and variant CJD related to post-industrial environmental contamination. World Leather, 2001, 14: 33-38
[60] Giese A, Levin J, Bertsch U, Kretzschmar H. Effect of metal ions on de novo aggregation of full-length prion protein. Biochem Biophys Res Commun, 2004, 320(4): 1240-1246
[61] Tsenkova RN, Iordanova IK, Toyoda K, Brown DR. Prion protein fate governed by metal binding. Biochem Biophys Res Commun, 2004, 325(3): 1005-1012
[62] Li R, Liu D, Zanusso C, Liu T, Fayen JD, Huang JH, Petersen RB, Gambetti R The expression and potential function of cellular prion protein in human lymphocytes. Cell Immunol, 2001,207(1):49-58.
[63] Reuter A, Binkle U, Stuermer CA, Plattner H. PrPc and reggies/flotillins are contained in and released via lipid-rich vesicles in Jurkat T cells. Cell Mol Life Sci. 2004, 61(16): 2092-9.
[64] Mattei V, Garofalo T, Misasi R, Circella A, Manganelli V, Lucania G, Pavan A, Sorice M. Prion protein is a component of the multimolecular signaling complex involved in T cell activation. FEBS Lett, 2004, 560(1-3): 14-8
[65] Mabbott NA, Young J, McConnell I, Bruce ME. Follicular dendritic cell dedifferentiation by treatment with an inhibitor of the lymphotoxin pathway dramatically reduces scrapie susceptibility. J Virol, 2003, 77(12): 6845-6854
[66] Gabus C, Auxilien S, Pechoux C, Dormont D, Swietnicki W, Morillas M, Surewicz W, Nandi P, Darlix JL. The prion protein has DNA strand transfer properties similar to retroviral nucleocapsid protein. J Mol Biol, 2001, 307(4): 1011-1021
[67] Gabus C, Derfington E, Leblanc P, Chnalderman J, Dormont D, Swietnicki W, Morillas M, Surewicz WK, Marc D, Nandi P, Darlix JL. The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-l. J Biol Chem, 2001,276(22): 19301-19309
[68] Whatley SA, Powell JF, Politopoulou C, Campbell IC, Brammer MJ, Percy NS. Regulation of intracellular free calcium levels by the cellular prion protein. Neuroreport, 1995, 6(17): 2333-2337
[69] Tobler I, Gaus SE, Deboer T, Achermann P, Fischer M, Rulicke T, Moser M, Oesch B, McBride PA, Manson JC. Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature, 1996, 380(6575): 639-642
[70] Low MG. The glycosyl-phosphatidylinositol anchor of membrane proteins. Biochim, Biophys Acta, 1989, 988(3): 427-454
[71] Borchelt DR, Rogers M, Stahl N, Telling G, Prusiner SB. Release of the cellular prion protein from cultured cells after loss of its glycoinositol phospholipid anchor. Glycobiology, 1993, 3(4):319-329
[72] Harris DA, Gorodinsky A, Lehmann S, Moulder K, Shyng SL. Cell biology of the prion protein. Curr Top Microbiol Immunol, 1996, 207:77-93
[73] Quaglio E, Chiesa R, Harris DA. Copper converts the cellular prion protein into a protease-resistant species that is distinct from the scrapie isoform. J Biol Chem, 2001, 276(14): 11432-11438
[74] Chiesa R, Piccardo P, Quaglio E, Drisaldi B, Si-Hoe SL, Takao M, Ghetti B, Harris DA. Molecular distinction between pathogenic and infectious properties of the priori protein. J Virol, 2003, 77(13): 7611-7622
[75] Bruce M. Strain typing studies of scrapie and BSE. In Methods in Molecular Medicine: Prion Diseases, 1996, pp. 223-236, Humana Press
[76] Scott M, Foster D, Mirenda C, Serban D, Coufal F, Walchli M, Torchia M, Groth D, Carlson G, DeArmond SJ, Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. Cell, 1989, 59: 847-857
[77] Prusiner SB, Groth D, Serban A, Koehler R, Foster D, Torchia M, Burton D, Yang SL, DeArmond SJ. Ablation of the priori protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies. Proc Natl Acad Sci USA, 1993, 90: 10608-10612
[78] Fischer M, Rulicke T, Raeber A, Sailer A, Moser M, Oesch B, Brandner S, Aguzzi A, Weissmann C. Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO J, 1996, 15: 1255-1264
[79] Lasmezas CI, Deslys JP, Robain O, Jaegly A, Beringue V, Peyrin JM, Fournier JG, Hauw JJ, Rossier J, Dormont D. Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science, 1997, 275: 402-405
[80] Manson JC, Jamieson E, Baybutt H, Tuzi NL, Barron R, McCormell I, Somerville R, Ironside J, Will R, Sy MS, Melton DW, Hope J, Bostock C. A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy. EMBO J, 1999, 18: 6855—6864
[81] Thackray AM, Klein MA, Aguzzi A, Bujdoso R. Chronic subclinical prion disease induced by low dose inoculum. J Virol, 2002, 76: 2510-2517
[82] Telling GC, Parchi P, DeArmond SJ, Cortelli P, Montagna P, Gabizon R, Mastrianni J, Lugaresi E, Gambetti P, and Prusiner SB. Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity. Science, 1996, 274 (5295):2079-82.
[83] Collinge J, Palmer MS, Sidle KC, Hill AF, Gowland I, Meads J, Asante E, Bradley R, Doey LJ, Lantos PL. Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature, 1995, 378: 779-783
[84] Scott MR, Safar J, Telling G, Nguyen O, Groth D, Torchia M, Koehler R, Tremblay P, Walther D, Cohen FE, DeArmond SJ, Prusiner SB. Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice. Proc Natl Acad Sci USA, 1997, 94: 14279-14284
[85] Buschmann A, Pfaff E, Reifenberg K, Muller HM, Groschup MH. Detection of cattle-derived BSE prions using transgenic mice overexpressing bovine PrP~c. Arch Virol, 2000, 16: 75-86
[86] Crozet C, Flamant F, Bencsik A, Aubert D, Samarut J, Baron T. Efficient transmission of two different sheep scrapie isolates in transgenic mice expressing the ovine PrP gene. J Virol, 2001, 75: 5328-5334
[87] Vilotte JL, Soulier S, Essalmani R, Stinnakre MG, Vaiman D, Lepourry L, Da Silva JC, Besnard N, Dawson M, Buscbmann A, Groschup M, Petit S, Madelaine MF, Rakatobe S, Le Dur A, Vilette D, Laude H. Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine PrP. J Virol, 2001, 75: 5977-5984
[88] Telling GC, Scott M, Mastrianni J, Gabizon R, Torchia M, Cohen FE, DeArmond SJ, Prusiner SB. Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell, 1995, 83(1): 79-90
[89] Crozet C, Bencsik A, Flamant F, Lezmi S, Samarut J, Baron T. Florid plaques in ovine PrP transgenic mice infected with an experimental ovine BSE. EMBO Rep, 2001, 2: 952-956
[90] Hill AF, Desbruslais M, Joiner S, Sidle KC, Gowland I, Collinge J, Doey LJ, Lantos P. The same prion strain causes vCJD and BSE. Nature, 1997, 389: 448-450
[91] Scott MR, Will R, Ironside J, Nguyen HO, Tremblay P, DeArmond SJ, Prusiner SB. Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci USA, 1999, 96: 15137-15142
[92] Race R, Chesebro B. Scrapie infectivity found in resistant species. Nature, 1998, 392: 770-777
[93] Race R, Raines A, Raymond GJ, Caughey B, Chesebro B. Long-term subclinical carrier state precedes scrapie replication and adaptation in a resistant species: analogies to Bovine Spongiform Encephalopathy and variant Creutzfeldt-Jakob disease in humans. J Virol, 2001, 75, 10106—10112
[94] Bruce ME, McConnell I, Fraser H, Dickinson AG. The disease characteristics of different strains of scrapie in Sine congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. J Gen Virol, 1991, 72: 595-603
[95] Fraser H. Murine scrapie strains, BSE models and genetics. In Sub-acute Spongiform Encephalopathies, 1991, pp. 131-136, Kluwer Academic Publishers, Brussels
[96] Lloyd SE, Linehan JM, Desbruslais M, Joiner S, Buckell J, Brandner S, Wadsworth JD, Collinge J. Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred mice. J Gen Virol, 2004, 85(8):2471-2478
[97] Lloyd SE, Uphill JB, Targonski PV, Fisher EM, Collinge J. Identification of genetic loci affecting mouse adapted bovine spongiform encephalopathy incubation time in mice. Neurogenetics, 2002, 4(2): 77-81
[98] Muramoto T, Kitamoto T, Tateishi J, Goto I. Successful transmission of Creutzfeldt-Jakob disease from human to mouse verified by prion protein accumulation in mouse brains. Brain Res. 1992, 599 (2): 309-316
[99] Glatzel M, Abela E, Maissen M, Aguzzi A. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Eng J Med, 2003, 349: 1812-1820
[100] Head MW, Ritchie D, Smith N, McLoughlin V, Nailon W, Samad S, Masson S, Bishop M, McCardle L, Ironside JW.. Peripheral tissue involvement in sporadic, iatrogenic, and variant Creutzfeldt-Jakob disease: an immunohistochemical, quantitative, and biochemical study. Am J Pathol, 2004, 164: 143-153
[101] Archer F, Bachelin C, Andreoletti O, Besnard N, Perrot G, Langevin C, Le Dur A, Vilette D, Baron-Van Evercooren A, Vilotte JL, Laude H. Cultured peripheral neuroglial cells are highly permissive to sheep prion infection. J Virol, 2004, 78(1): 482-90
[102] Parchi P, Gambetti P. Human prion diseases. Curt Opin Neurol, 1995, 8(4): 286-93
[103] Rubenstein R, Carp RI, Callahan SM. In vitro replication of scrapie agent in a neuronal model: infection of PC12 cells. J Gen Virol, 1984, 65 (Pt 12): 2191-2198
[104] Schatzl HM, Laszlo L, Holtzman DM, Tatzelt J, DeArmond SJ, Weiner RI, MoNey WC, Prusiner SB. A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis. J Virol, 1997, 71(11): 8821-8831
[105] Brown DR, Clive C, Haswell SJ. Antioxidant activity related to copper binding of native prion protein. J Neurochem, 2001, 76(1): 69-76
[106] Rieger R, Edenhofer F, Lasmezas CI, Weiss S. The human 37-kDa laminin receptor precursor interacts with the priori protein in eukaryotic cells. Nat Med, 1997, 3(12): 1383-8
[107] Forloni G, Angeretti N, Chiesa R, Monzani E, Salmona M, Bugiani O, Tagliavini F. Neurotoxicity ofa prion protein fragment. Nature, 1993, 362(6420): 543-546
[108] Brown DR, Schmidt B, Kretzschmar HA. A priori protein fragment primes type 1 astrocytes to proliferation signals from microglia. Neurobiol Dis, 1998, 4(6): 410-422
[109] Thellung S, Florio T, Corsaro A, Arena S, Merlino M, Salmona M, Tagliavini F, Bugiani O, Forloni G, Schettini G. Apoptotic cell death and impairment of L-type voltage-sensitive calcium channel activity in rat cerebellar granule cells treated with the prion protein fragment 106-126. Neurobiol Dis, 2000, 7(4): 299-309
[110] White AR, Guirguis R, Brazier MW, Jobling MF, Hill AF, Beyreuther K, Barrow CJ, Masters CL, Collins SJ, Cappai R. Sublethal concentrations of prion peptide PrP106-126 or the amyloid beta peptide of Alzheimer's disease activates expression of proapoptotic markers in primary cortical neurons. Neurobiol Dis, 2001, 8(2): 299-316
[111] Bonetto V, Massignan T, Chiesa R, Morbin M, Mazzoleni G, Diomede L, Angeretti N, Colombo L, Forloni G, Tagliavini F, Salmona M. Synthetic miniprion PrP106. J Biol Chem, 2002, 277(35): 31327-32334
[112] Salmona M, Malesani P, De Gioia L, Gorla S, Bruschi M, Molinari A, Della Vedova F, Pedrotti B, Marrari MA, Awan T, Bugiani O, Forloni G, Tagliavini F. Molecular determinants of the physicochemical properties of a critical prion protein region comprising residues 106-126. Biochem J, 1999, 342 (1): 207-214
[113] Ragg E, Tagliavini F, Malesani P, Monticelli L, Bugiani O, Forloni G, Salmona M. Determination of solution conformations of PrP106-126, a neurotoxic fragment of prion protein, by lH NMR and restrained molecular dynamics. Eur J Biochem, 1999, 266(3): 1192-201
[114] Diomede L, Bizzi A, Magistrelli A, Modest EJ, Salmona M, Noseda A. The prion protein and cellular cholesterol homestasis. Neurobiol Lipids, 2002, 3(1): 8-14
[115] Caughey B, Raymond LD, Raymond GJ, Maxson L, Silveira J, Baron GS. Inhibition of protease resistant prion protein accumulation in vitro by curcumin. J Virol, 2003, 77(9):5499-5502
[116] Chung HW. Reverse transcriptase PCR (RT-PCR) and quantitative competitive PCR (QC-PCR). Exp Mol Med, 2001, 33: 85-97
[117] Giulietti A, Overbergh L, Valckx D, Decallonne B, Bouillon R, Mathieu C. An overview of real-time quantitative PCR: application to quantify cytokine gene expression. Methods, 2001, 25(4): 386-401
[118] Heid C A, Stevens J, Livak KJ, Williams PM. Real-time quantitative PCR. Genome Res, 1996, 6 (10): 986-994
[119] Kariyazono H, Ohno T, Thara K, Igarashi H, Joh-o K, Ishikawa S, Hara T. Rapid detection of the 22q11-2 deletion with quantitative real time PCR. Mol Cell Probes, 2001, 15(2): 71-73
[120] Tondella ML, Talkington DF, Holloway BP, Dowell SF, Cowley K, Soriano-Gabarro M, Elkind MS, Fields BS. Development and evaluation of real time PCR based fluorescence assays for detection of Chlamydia pneumonia. J Clin Microbiol, 2002, 40(2): 575-583
[121] Stults JR, Snoeyenbos West O, Methe B, Lovley DR, Chandler DP. Application of the 5' fluorogenic exonuclease assay (Taqman) for quantitative ribosomal DNA and rRNA analysis in sediments. Appl Environ Microbiol, 2001, 67(6): 2781-2789
[122] Matera G, Lamberti A, Quirino A, Foca D, Giancotti A, Barreca GS, Guadagnino V, Liberto MC. Changes in the prevalence of hepatitis C virus(HCV) genotype 4 in Calabria, Southern Italy. Diagn Microbiol Infect Dis, 2002, 42(3):169-173
[123] Helps C, Reeves N, Tasker S, Harbour D. Use of real time quantitative PCR to detect Chlamydophila felis infection. J Clin Microbiol, 2001, 39(7): 2675-2676
[124] Loeffler J, Henke N, Hebart H, Schmidt D, Hagmeyer L, Schumacher U, Einsele H. Quantification of fungal DNA by using fluorescence resonance energy transfer and the light cycler system. J Clin Microbiol, 2000, 38: 586-590
[125] Eckert C, Landt O, Taube T, Seeger K, Beyermann B, Proba J, Henze G. Potential of Lightcycler technology for quantification of minimal residulal disease in childhood acute lymphoblastic leukemia. Leukemia, 2000, 14: 316-323
[126] Kearns AM, Turner AJ, Eltfingham GJ, Freeman R. Rapid detection and quantification of CMV DNA in urine using LightCycler based real-time PCR. J Clin Virol, 2002, 24(1 2): 131-134
[127] Harder TC, Hufnagel M, Zahn K, Beutel K, Schmitt HJ, Ullmann U, Rautenberg P. New Lightcycler PCR for rapid and sensitive quantification of parvovirus B19 DNA guides therapeutic decision making in relapsing infections. J Clin Microbiol, 2001, 39(12): 4413-4419
[128] Bertsch T, Zimmer W, Casarin W, Denz C, Quintel M, Fassbender K. Real-time PCR assay with fluorescent hybridization probes for rapid interleukin 6 promoter genotyping. Clin Chem, 2001, 47: 1873-1874
[129] Yin JL, Shackel NA, Zekry A, McGuinness PH, Richards C, Putten KV, McCaughan GW, Eris JM, Bishop GA. Real time reverse transcriptase polymerase Chain reaction (RT-PCR) for measurement of cytokine and growth factor mRNA expression with fluorogenic probes or SYBRG green I Immunol Cell Biol, 2001, 79(3): 213-221
[130] Lie YS, Petropoulos CJ. Advances in quantitative PCR technology: 5'nuclease assays [J]. Curr Opin Biotechnol, 1998, 9(1): 43-48.
[131] Tyagi S, Bratu DP, Kramer F R. Multicolor molecular beacons for allele discrimination [J]. Nat Biotechnol, 1998, 16(1): 49-53
[132] Whitcombe D, Theaker J, Guy SP, Brown T, Little S. Detection of PCR Products using self-probing amplicons and fluorescence[J]. Nat Biotechnol, 1999, 17(8): 804-807
[133] Becker K, Pan D, Whitely CB. Real-time quantitative polymerase chain reaction to assess gene transfer. Hum Gene Ther, 1999, 10: 2559-2566
[134] Wang X, Li X, Willette RN, Barone FC, Feuerstein GZ. Application of real-time polymerase chain reaction to quantitate induced expression of interleukin-l beta mRNA in ischemic brain tolerance. Neurosci Res, 2000, 59: 238-246
[135] Gibson UE, Heid CA, Williams PM. A novel methods for real time quantitative RT-PCR. Genome Res, 1996, 6: 995-1001
[136] Egawa C, Miyoshi Y, Takamura Y, Taguchi T, Tamaki Y, Noguchi S. Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancer. Int J Cancer, 2001, 95:255-259
[137] Leith CP, Kopecky KJ, Chen IM, Eijdems L, Slovak ML, McConnell TS, Head DR, Weick J, Grever MR, Appelbaum FR, Willman CL. Frequency and clinical significance of the expression of the multidrug resistance proteins MDRl/P glycoprotein, MRPl and LRP in acute myeloid leukemia: a a southwest oncology group study. Blood, 1999, 94(3): 1086-1099
[138] Nuessler V, Stotzer O, Gullis E, Pelka-Fleischer R, Pogrebniak A, Gieseler F, Wilmanns W. Bcl-2, Bax and bcl-xL expression in human sensitive and resistant leukemia cell lines. Leukemia, 1999, 13 (11): 1864-1872
[139] Witham PK Yamashiro CT, Livak KJ, Batt CA. A PCR-based assay for the detection of Escherichia coli Shiga-like toxin genes in ground beef. Appl Environ Microbiol, 1996 62(4): 1347-1353
[140] Chen S, Yee A, Griffiths M, Larkin C, Yamashiro CT, Behari R, Paszko-Kolva C, Rahn K, De Grandis SA. The evaluation of a fluorogenic polymerase chain reaction assay for the detection of Salmonella species in food commodities. Int J Food Microbiol, 1997, 35(3): 239-250
[141] Desjardin LE, Chen Y, Perkins MD, Teixeira L, Cave MD, Eisenach KD. Comparison of the ABI 7700 system (TaqMan) and competitive PCR for quantification of IS6110 DNA in sputum during treatment of tuberculosis. J Clin Microbiol, 1998, 36(7): 1964-1968.
[142] Griscelli F, Barrois M, Chauvin S, Lastere S, Bellet D, Bourhis JH. Quantification of human cytomegalovirus DNA in bone marrow transplant recipients by real-time PCR. J Clin Microbiol, 2001, 39(12): 4362-4369
[143] Walburger DK, Afonina IA, Wydro R. An improved real time PCR method for simultaneous detection of C282Y and H63D mutations in the HFE gene associated with hereditary hemochromatosis. Murat Res, 2001, 15: 121-127
[144] Parks SB, PoPovich BW, Press RD. Real-time polymerase chain reaction with fluorescent hybridization probes for the detection of prevalent mutations causing common thrombophilic and iron overload phenotypes. Am J Clin Pathol, 2001, 115: 439-437
[145] Coasts B, Girodon E, Vidaud D, Flori E, Ardalan A, Conteville P, Fanen P, Niel F, Vidaud M, Goosens M. Prenatal detection by real-time quantitative PCR and characterization of a new CFTR deletion, 3600+15kbde115.3kb (or CFTRdlel9). Clin Chem, 2000, 46: 1417-1420
[146] Lo YM, Lau TK, Zhang J, Leung TN, Chang AM, Hjelm NM, Elmes RS, Bianchi DW. Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21. Clin Chem, 1999, 45: 1745-1751
[147] Paradis V, Laurent A, Flejou JF, Vidaud M, Bedossa P. vidence for the polyclonal nature offocal nodular hyperplasia of the liver by the study of X chromosome inactivation. Hepatology, 1997, 26 (4): 891-895
[148] Dolken L, Schuler F, Dolken G. Quantitative detection of t (14; 18) positive cells by real time quantitative PCR using fluorogenic probes. Biotechniques, 1998, 25(6): 1058-1064
[149] Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, McCardle L, Chree A, Hope J, Birkett C, Cousens S, Fraser H, Bostock CJ. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature, 1997, 389: 498-501
[150] Prusiner S B. Prions. Proc Natl Acta Sci USA, 1998, 95: 13363-13383
[151] Kimberlin RH, Walker CA. Pathogenesis of scrapie (strain 263K) in hamsters infected intracerebrally, intraperitoneally or intraocularly. J Comp Pathol, 1986, 67: 255-263
[152] Aguzzi A, Heppner FL, Heikenwalder M, Prinz M, Mertz K, Seeger H, Glatzel M. Immune system and peripheral nerves in propagation of prions to CNS. Br Med Bull, 2003, 66: 141-159
[153] Terry LA, Marsh S, Ryder SJ, Hawkins SA, Wells GA, Spencer YI. Detection of disease-specific PrP in the distal ileum of cattle exposed orally to the agent of bovine spongiform encephalopathy. Vet Rec, 2003, 152(13): 387-92.
[153] McBride PA, Schulz-Schaeffer WJ, Donaldson M, Bruce ME, Diringer H, Kretzschmar HA, Beekes M. Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves. J Virol, 2001, 75: 9320-9327
[154] Prinz M, Huber G, Macpherson AJ, Heppner FL, Glatzel M, Eugster HP, Wagner N, Aguzzi A. Oral prion infection requires normal numbers of Payer's patches but not of enteric lymphocytes. Am J Pathol, 2003, 162(4): 1103-1111
[155] Prinz M, Heikenwalder M, Junt T, Schwarz P, Glatzel M, Heppner FL, Fu YX, Lipp M, Aguzzi A. Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion. Nature, 2003, 425(6961): 957-962.
[156] Walker N J. Real-time and quantitative PCR: applications to mechanism-based toxicology. J Biochem Mol Toxicol, 2001, 15(3):v121-127.
[157] Seung-I choi, Won-Kyu Ju, Eun-Kyoung Choi Jin Kim. Mitochondrial dysfunction induced by oxidative stress in the brain of hamsters infected with the 263K scrapie agent. Acta Neuropathol, 1998, 96: 279-786.
[158] 孙宪锋,张保云,董小平,等.Scrapie 263K毒株感染金黄地鼠及对其脑组织的组织学研究.病毒学报,2001,16:48-53
[159] 张宝云,侯星生,高晨,等.羊瘙痒病小鼠适应株139A可突破种属屏障颅内感染金黄地鼠.病毒学报,2002,18(4):337-341
[160] 梅英,刘长安,龚建平.定量PCR的研究进展.国外医学临床生物化学与检验学分册,2004,25(1):23-26
[161] van der Velden V H, Hochhaus A, Cazzaniga C. et al. Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: Principles, approaches, and laboratory aspects. Leukemia, 2003, 17(6): 1013-1034
[162] 安靓.医学发育生物学(第一版).北京:人民卫生出版社,2002:101-129
[163] Mehlhom I, Groth D, Stockel J, Moffat B, Reilly D, Yansura D, Willett WS, Baldwin M, Fletterick R, Cohen FE, Vandlen R, Henner D, Prusiner SB. High-level expression and characterization of a purified 142-residue polypeptide of the prion protein. Biochemistry, 1996, 35(17):5528-5537
[164] Hill AF, Antoniou M, Collinge J. Protease-resistant prion protein produced in vitro lacks detectable infectivity. J Gen Virol, 1999, 80 (1): 11-14
[165] Van Everbroeck B, Pals P, Martin JJ, Cras P. Transmissible spongiform encephaiopathies: the story of a pathogenic protein. Peptides, 2002, 23, 1351-1359
[166] Legname G, Baskakov Ⅳ, Nguyen HO, Riesner D, Cohen FE, DeArmond SJ, Prusiner SB. Synthetic mammalian prions. Science, 2004, 305(5684): 673-676
[167] Vorberg I, Priola SA. Molecular basis of scrapie strain glycoform variation. J Biol Chem 2002, 277: 36775-36781
[168] Baskakov Ⅳ, Legname G, Baldwin MA, Prusiner SB, Cohen FE. Pathway complexity of prion protein assembly into amyloid. J. Biol. Chem, 2002, 277(24): 21140-21148
[169] Liu T, Zwingman T, Li R, Pan T, Wong BS, Petersen RB, Gambetti P, Herrup K, Sy MS. Differential expression of cellular prion protein in mouse brain as detected with multiple anti-PrP monoclonal antibodies. Brain Res. 2001, 896(1-2): 118-129.
[170] 鄂征.组织培养和分子细胞学技术.北京出版社,1999
[171] 莫永炎,姜永,陈瑗.大脑星形胶质细胞生物学功能研究进展.生理科学进展,2002,33:71-73
[172] Yang J C, Shan J, Ng K F, et al. Morphine and methadone have different effects on calcium channel currents. Brain Res, 2000, 87(1-2): 199-203
[173] Olliver Milhavet, Sylvain Lehmann. Oxidative stress and the prion protein in transmissible spongiform encephalopathies. Brain Research Review, 2002, 38: 328-339
[174] Isabelle Sponne, Alexandre Fifre, Violette Koziel, et al. Humanin rescues cortical neurons from prion-peptide-induced apoptosis. Mol Cell Neurosci, 2004, 25: 95-102
[175] 王省,蔡新华,孙银平.大鼠小脑皮质颗粒神经元的形态和分布.解剖科学进展,2002,8(3):203-04
[176] Yan GM, Irwin RP, Lin SZ, Weller M, Wood KA, Paul SM. Diphenylhydantoin induces apoptotic cell death of cultured rat cerebellar granule neurons. J Pharmaco Exp Ther, 1995, 274: 983-990
[177] McCarthy KD, Vellis JD. Preparation of separation astroglial and oligdendroglial cell culture from rat cerebral tissue. J Cell Biol, 1980, 85: 890-902
[178] Das GD, Hallas BH, Das KG. Transplantation of brain tissue in the brain of rat, 1. Growth characteristics of neocortical transplants from embryos of different ages. Am J Anat, 1980, 158: 135-145
[179] 忘伯沄,李玉松,黄高昇主编.病理学技术,人民卫生出版社,2001:178-179
[180] 王新亭,徐以明.显示神经元的银浸改良法.解剖学杂志,1994,17(6):557-559
[181] 李文明,苏兴文,邱鹏新等.高钾可以诱导培养的小脑颗粒神经元凋亡.中国神经科学杂志,2001,17(1):88-100
[182] 薛庆善,郭畹华.大鼠大脑皮质星形胶质细胞的体外培养及其促神经突起生长作用研究.神经解剖学杂志,1999,12(2):151-155
[183] Barbin G, Selak I and Manthorpe M. Use of central neuronal cultures for the detection of neuron notrophic agents. Neuroscience, 1984, 12: 33-43
[184] Anderson CNG, Tolkovsky AM. A role for MAPK/ERK in sympathetic neuron survival: protection against a p53-dependent, JNK-independent induction of apoptosis by cytosine arabinoside. J Neurosci, 1999: 664-670
[185] Glub M S, Han B, Keen C L. Aluminum uptake and effects on transferring mediated iron uptake in primary cultures of rat neurons, Astrocytes and oligodendrocytes. Neurotoxicology, 2002, 20(6): 961-970
[186] Benoit Schneider, Vincent Mutel, Mathea Pietri, et al. NADPH oxidase and extracelluar-regulated kinases 1/2 are targets of prion protein signaling in neuronal and nonneuronal cells. PNAS, 2003, 100:13326-13331
[187] Kimelberg H K. Receptors on astrocytes-what possible function? Neurochem Int, 1995, 26(1): 27-40
[188] Prusiner SB. Chemistry and biology of prions. Biochemistry, 1992, 31 (49): 12277-12288.
[189] Collinge J. Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci, 2001, 24: 519-550.
[190] Chiesa R, Harris D A. Prion diseases: what is the neurotoxic molecule? Neurobiol Dis, 2001, 8(5): 743-763
[191] Chen SG, Teplow DB, Parchi P, et al. Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem, 1995, 270(32): 19173-19180.
[192] Florio T, Thellung S, Amico C, et al. Prion protein fragment 106-126 induces apoptotic cell death and impairment of L-type voltage-sensitive calcium channel activity in the GH3 cell line. J Neurosci Res, 1998, 54(3): 341-352
[193] Brown DR, Schmidt B, Kretzschmar H A, Role of microglia and host prion protein in neurotoxicity of a prion protein fragment. Nature, 1996, 380: 345-347
[194] Rymer D L, Good TA. The role of prion peptide structure and aggregation in toxicity and membrane binding. J Neurochem, 2000, 75(6): 2536-2545.
[195] Ettaiche M, Pichot R, Vincent JP, et al. In vivo cytotoxicity of the prion protein fragment 106-126. J Biol Chem, 2000, 275(47): 36487-36490
[196] Brown D R. PrPSc-like prion protein peptide inhibits the function of cellular prion protein. Biochem J, 2000, 352: 511-518.
[197] Lin MC, Mirzabekov T, Kagan BL. Channel formation by a neurotoxic prion protein fragment. J Biol Chem, 1997, 272 (1): 44-47
[198] Manunta M, Kunz B, Sandmeier E, Christen P, Schindler H. Reported channel formation by prion protein fragment 106-126 in planar lipid bilayers cannot be reproduced. FEBS Lett, 2000, 474(2-3): 255-256
[199] Zanata SM, Lopes MH, Mercadante AF, Hajj GN, Chiarini LB, Nomizo R, Freitas AR, Cabral AL, Lee KS, Juliano MA, de Oliveira E, Jachieri SG, Burlingame A, Huang L, Linden R, Brentani RR, Martins VR. Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection. EMBO J, 2002, 21: 3307-3316
[200] Forloni G, Angeretti N, Smiroldo S. Neuroprotective activity of acetyl-L-carnitine: studies in vitro. J Neurosci Res, 1994, 37(1): 92-96
[201] Raeber AJ, Race RE, Brandner S, Priola SA, Sailer A, Bessen RA, Mucke L, Manson J, Aguzzi A, Oldstone MB, Weissmann C, Chesebro B. Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. EMBO J, 1997, 16 (20): 6057-6065
[202] Chabry J, Ratsimanohatra C, Sponne I, Elena PP, Vincent JP, Pillot T. In vivo and in vitro neurotoxicity of the human prion protein (PrP) fragment P118-135 independently of PrP expression. J Neurosci, 2003, 23: 462-469
[203] Diedrich JF, Bendheim PE, Kim YS, Carp RI, Haase AT. Scrapie-associated prion protein accumulates in astrocytes during scrapie infection. Proc Natl Acad Sci USA, 1991, 88(2): 375-379.
[204] Tagliavini F, Forloni G, D'Ursi P, Bugiani O, Salmona M. Studies on peptide fragments of prion proteins. Adv Protein Chem, 2001, 57: 171-201
[205] Shmerling D, Hegyi I, Fischer M, Blattler T, Brandner S, Gotz J, Rulicke T, Flechsig E, Cozzio A, von Mering C, Hangartner C, Aguzzi A, Weissmann C. Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell, 1998, 93: 203-214.
[206] Zahn R, Liu A, Luhrs T, Rick R, von Schroetter C, Lopez Garcia F, Billeter M, Calzolai L, Wider G, Wuthrich K. NMR solution structure of the human prion protein. Proc. Natl Acad Sci USA, 2000, 97(1): 145-150
[2] Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science, 1982, 216: 136-144
[3] Chiarini LB, Freitas AR, Zanata SM, Brentani RR, Martins VR, Linden R. Cellular prion protein transduces neuroprotective signals. EMBO J, 2002, 21, 3317-3326
[4] Zou WQ, Zheng J, Gray DM, Gambetti P, Chen SG. Antibody to DNA detects scrapie but not normal priori protein. Proc Natl Acad Sci USA, 2004, 101: 1380-1385
[5] Adler V, Zeiler B, Kryukov V, Kascsak R, Rubenstein R, Grossman A. Small, highly structured RNAs participate in the conversion of human recombinant PrPsen to PrPres in vitro. J Mol Biol, 2003, 332: 47-57
[6] McBride PA, Eikelenboom P, Kraal G, Fraser H, Bruce ME. PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. J Pathol, 1992, 168(4): 413-418
[7] Humphrey JH, Grennan D, Sundaram V. The origin of follicular dendritic cells in the mouse and the mechanism of trapping of immune complexes on them. Eur J Immunol, 1984, 14(9): 859-864
[8] Montrasio F, Cozzio A, Flechsig E, Rossi D, Klein MA, Rulicke T, Raeber A J, Vosshenrich CA, Proft J, Aguzzi A, Weissmann C. B lymphocyte-restricted expression of prion protein does not enable prion replication in priori protein knockout mice. Proc Natl Acad Sci U S A, 2001, 98 (7): 4034-4037
[9] Bencsik A, Lezmi S, Hunsmann G, Baron T. Close vicinity of PrP expressing cells (FDC) with noradrenergic fibers in healthy sheep spleen. Dev Immunol, 2001, 8(3-4): 235-241
[10] Glatzel M, Giger O, Braun N, Aguzzi A. The peripheral nervous system and the pathogenesis of prion diseases. Curr Mol Med, 2004, 4(4): 355-359
[11] Beekes M, McBride PA. Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie. Neurosci Lett, 2000, 278(3): 181-184
[12] Houston F, Foster JD, Chong A, Hunter N, Bostock CJ. Transmission of BSE by blood transfusion in sheep. Lancet, 2000, 356(9234): 999-1000
[13] Fischer MB, Roeckl C, Parizek P, Schwarz HP, Aguzzi A. Binding of disease-associated prion protein to plasminogen. Nature, 2000, 408(6811): 479-483
[14] Singh N, Gu Y, Bose S, Kalepu S, Mishra RS, Verghese S. Prion peptide 106-126 as a model for prion replication and neurotoxicity. Front Biosci, 2002, 7: 60-71
[15] Ciesielski-Treska J, Grant NJ, Ulrich G, Corrotte M, Bailly Y, Haeberle AM, Chasserot-Golaz S, Bader MF. Fibrillar prion peptide (106-126) and scrapie prion protein hamper phagocytosis in microglia. Glia, 2004, 46(2): 101-115
[16] Kaneider NC, Kaser A, Dunzendorfer S, Tilg H, Patsch JR, Wiedermann CJ. Neurokinin-l receptor interacts with PrP (106-126)-induced dendritic cell migration and maturation. J Neuroimmunol, 2005, 158(1-2): 153-158
[17] Haik S, Peyrin JM, Lins L, Rosseneu MY, Brasseur R, Langeveld JP, Tagliavini F, Deslys JP, Lasmezas C, Dormont D. Neurotoxicity of the putative transmembrane domain of the prion protein. Neurobiol Dis, 2000, 7: 644-656
[18] Fabrizi C, Silei V, Menegazzi M, Salmona M, Bugiani O, Tagliavini F, Suzuki H, Lauro GM. The stimulation of inducible nitric-oxide synthase by the priori protein fragment 106—126 in human microglia is tumor necrosis factor-alpha-dependent and involves p38 mitogen-activated protein kinase. J Biol Chem, 2001, 276(28): 25692-25696
[19] Kourie JI. Mechanisms of prion-induced modifications in membrane transport properties: implications for signal transduction and neurotoxicity. Chem Biol Interact, 2001, 138(1): 1-26
[20] Requena JR, Dimitrova MN, Legname G, Teijeira S, Prusiner SB, Levine RL. Oxidation of methionine residues in the prion protein by hydrogen peroxide. Arch Biochem Biophys, 2004, 432(2): 188-195
[21] Kourie JI, Farrelly PV, Henry CL. Channel activity of deamidated isoforms of prion protein fragment 106-126 in planar lipid bilayers. J Neurosci Res, 2001, 66(2): 214-220
[22] Agostinho P, Oliveira CR. Involvement of calcineurin in the neurotoxic effects induced by amyloid-beta and prion peptides. Eur J Neurosci, 2003, 17(6): 1189-1196
[23] Roucou X, Gains M, LeBlanc AC. Neuroprotective functions of priori protein. J Neurosci Res, 2004, 75: 153-161
[24] Wong BS, Pan T, Liu T, Li R, Petersen RB, Jones IM, Gambetti P, Brown DR, Sy MS. Prion disease: a loss of antioxidant function? Biochem Biophys Res Commun, 2000, 275: 249-252
[25] Caughey B, Raymond G J, Callahan MA, et al. Interactions and conversions of prion protein isoforms. Adv Protein Chem, 2001, 57: 139-169
[26] Hadlow W J. Scrapie and kuru. Lancet, 1959, 2: 289-290
[27] Chandler R L. Encephalopathy in mice produced by inoculation with scrapie brain material. Lance, 1961, 1: 1378-1379
[28] Alper T, Haig DA, Clarke MC. The exceptionally small size of the scrapie agent. Biochemistry and Biophysics Research Communications, 1966, 22: 278-284
[29] Alper T, Cramp WA, Haig DA, Clarke MC. Does the agent of scrapie replicate without nucleic acid? Nature, 1967, 214: 764-766
[30] Dickinson AG, Outram GW. The scrapie replication-site hypothesis and its implications for pathogenesis. In: PRUSINER SB & HADLOW WJ, (Eds). Slow transmissible diseases of the nervous system. Academic Press, New York, 1979, 2: 13-31
[31] Besnoit MM, Morel Ch. Note sur les lesions nerveuses de la tremblante du mouton. Revue Vet Prinaire, 1998, ⅹⅹⅢ (LV), 27-400
[32] Aucouturier P, Carp RI, Carnaud C, Wisniewski T. Prion diseases and the immune system. Clin Immunol, 2000, 96: 79-85
[33] Cashman NR, Loertscher R, Nalbantoglu J, Shaw I, Kascsak RJ, Bolton DC, Bendheim PE. Cellular isoform of the scrapie agent protein participates in lymphocyte activation. Cell, 1990, 61: 185-92
[34] Hope J, Shearman M S, Baxter H C, et al. Cytotoxicity of prion protein peptide (PrP106-126) differs in mechanism from the cytotoxic activity of the Alzheimer's disease amyloid peptide, A beta 25-35. Neurodegeneration, 1996, 5(1): 1-11
[35] Kawahara M, Kuroda Y, Arispe N, et al. Alzheimer's beta-amyloid, human islet amylin, and prion protein fragment evoke intracellular free calcium elevations by a common mechanism in a hypothalamic GnRH neuronal cell line. J Biol Chem, 2000, 275(19): 14077-14083
[36] Mouillet-Richard S, Ermonval M, Chebassier C, Laplanche JL, Lehmann S, Launay JM, Kellermann O. Signal transduction through prion protein. Science, 2000, 289: 1925-1928
[37] Brown D R. Role of the prion protein in copper turnover in astrocytes. Neurobiol Dis, 2004, 15(3): 534-543
[38] Glatzel M, Aguzzi A. PrP(C) expression in the peripheral nervous system is a determinant of prion neuroinvasion. J Gen Virol, 2000, 81: 2813-2821
[39] Zanusso G, Liu D, Ferrari S, Hegyi I, Yin X, Aguzzi A, Hornemann S, Liemann S, Glockshuber R, Manson JC. Prion proteinexpression in different species: analysis with a panel of new mAbs. Proc Natl Acad Sci USA, 1998, 5: 8812-8816
[40] Robakis NK, Sawh PR, Wolfe GC, Rubenstein R, Carp RI, Irmis MA. Isolation of a cDNA clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues. Proc Natl Acad Sci USA, 1986, 83: 6377-6381
[41] Harris DA, Lele P, Snider WD. Localization of the mRNA for a chicken prion protein by in situ hybridization. Proc Natl Acad Sci USA, 1993, 90: 4309-4313
[42] Harris DA, Falls DL, Johnson FA, Fischbach GD. A prion-like protein from chicken brain copurifies with an acetylcholine receptor-inducing activity. Proc Natl Acad Sci USA, 1991, 88:7664-7668
[43] Ford MJ, Burton LJ, Morris RJ, Hall SM. Selective expression of prion protein peripheral tissues of the adult mouse. Neuroscience, 2002, 113(1): 177-192
[44] Tichopad A, Pfaffl MW, Didier A. Tissue-specific expression pattern of bovine prion gene: quantification using real-time RT-PCR. Molecular and Cellular Probes, 2003, 17: 5-10
[45] Selvaggini C, De Gioia L, Cantu L, Ghibaudi E, Diomede L, Passerini F, Forloni G, Bugiani O, Tagliavini F, Salmona M. Molecular characteristics of a protease-resistant, amyloidogenic and neurotoxic peptide homologous to residues 106-126 of the prion protein. Biochem Biophys Res Commun, 1993, 194(3): 1380-1386.
[46] Gu Y, Fujioka H, Mishra R S, et al. Prion peptide 106-126 modulates the aggregation of cellular prion protein and induces the synthesis of potentially neurotoxic transmembrane PrP. J Biol Chem. 2002, 277: 2275-2286.
[47] Stewart RS, Drisaldi B, Harris DA. A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic Reticulum. Mol Biol Cell, 2001, 12(4): 881-889
[48] Pan T, Li R, Wong BS, Liu T, Gambetti P, Sy MS. Heterogeneity of normal prion protein in twodimensional immunoblot: presence of various glycosylated and truncated forms. J Neurochem, 2002, 81(5): 1092-101
[49] Caughey B, Neary K, Buller R, Ernst D, Perry LL, Chesebro B, Race RE. Normal and scrapieassociated forms of prion protein differ in their sensitivities to phospholipase and proteases in intact neuroblastoma cells. J Virol, 1990, 64(3): 1093-101.
[50] Borchelt DR, Lee MK, Slunt HS, Guarnieri M, Xu ZS, Wong PC, Brown RH Jr, Price DL, Sisodia SS, Cleveland DW. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc Natl Acad Sci US A, 1994, 91 (17): 8292-6.
[51] Sabuncu E, Petit S, Le Dur A, Lan Lai T, Vilotte JL, Laude H, Vilette DPrP polymorphisms tightly control sheep prion replication in cultured cells. J Virol, 2003, 77 (4): 2696-700.
[52] Brown DR. Prion and prejudice: normal protein at the synapse. Trends Neurosci, 2001, 24: 85-90[53] Brown DR. Copper and prion disease Brain Res Bull, 2001, 55: 165-173
[54] Bouzamondo-Bemstein E, Hopkins SD, Spilman P, Uyehara-Lock J, Deering C, Safar J, Prusiner SB, Ralston HJ 3rd, DeArmond SJ. The neurodegeneration sequence in prion diseases: evidence from functional, morphological and ultrastructural studies of the GABA ergic system. J Neuropathol Exp Neurol, 2004, 63(8): 882-99.
[55] Collinge J, Whittington MA, Sidle KC, Smith CJ, Palmer MS, Clarke AR, Jefferys JG. Prion protein is necessary for normal synaptic function. Nature, 1994, 370(6487): 295-7.
[56] Karmenberg K, Groschup MH, Sigel E. Cellular prion protein and GABAA receptors: no physical association? Neuroreport, 1995, 7(1): 77-80.
[57] Lu P, Sturman JA, Bolton DC. Altered GABA distribution in hamster brain is an early molecular consequence of infection by scrapie prions. Brain Res, 1995, 681(1-2): 235-41.
[58] Sakaguchi S, Katamine S, Nishida N, Moriuchi R, Shigematsu K, Sugimoto T, Nakatani A, Kataoka Y, Houtani T, Shirabe S, Okada H, Hasegawa S, Miyamoto T, Noda T. Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene. Nature, 1996, 380(6574): 528-531.
[59] Brown DR. An alternative cause for BSE and variant CJD related to post-industrial environmental contamination. World Leather, 2001, 14: 33-38
[60] Giese A, Levin J, Bertsch U, Kretzschmar H. Effect of metal ions on de novo aggregation of full-length prion protein. Biochem Biophys Res Commun, 2004, 320(4): 1240-1246
[61] Tsenkova RN, Iordanova IK, Toyoda K, Brown DR. Prion protein fate governed by metal binding. Biochem Biophys Res Commun, 2004, 325(3): 1005-1012
[62] Li R, Liu D, Zanusso C, Liu T, Fayen JD, Huang JH, Petersen RB, Gambetti R The expression and potential function of cellular prion protein in human lymphocytes. Cell Immunol, 2001,207(1):49-58.
[63] Reuter A, Binkle U, Stuermer CA, Plattner H. PrPc and reggies/flotillins are contained in and released via lipid-rich vesicles in Jurkat T cells. Cell Mol Life Sci. 2004, 61(16): 2092-9.
[64] Mattei V, Garofalo T, Misasi R, Circella A, Manganelli V, Lucania G, Pavan A, Sorice M. Prion protein is a component of the multimolecular signaling complex involved in T cell activation. FEBS Lett, 2004, 560(1-3): 14-8
[65] Mabbott NA, Young J, McConnell I, Bruce ME. Follicular dendritic cell dedifferentiation by treatment with an inhibitor of the lymphotoxin pathway dramatically reduces scrapie susceptibility. J Virol, 2003, 77(12): 6845-6854
[66] Gabus C, Auxilien S, Pechoux C, Dormont D, Swietnicki W, Morillas M, Surewicz W, Nandi P, Darlix JL. The prion protein has DNA strand transfer properties similar to retroviral nucleocapsid protein. J Mol Biol, 2001, 307(4): 1011-1021
[67] Gabus C, Derfington E, Leblanc P, Chnalderman J, Dormont D, Swietnicki W, Morillas M, Surewicz WK, Marc D, Nandi P, Darlix JL. The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-l. J Biol Chem, 2001,276(22): 19301-19309
[68] Whatley SA, Powell JF, Politopoulou C, Campbell IC, Brammer MJ, Percy NS. Regulation of intracellular free calcium levels by the cellular prion protein. Neuroreport, 1995, 6(17): 2333-2337
[69] Tobler I, Gaus SE, Deboer T, Achermann P, Fischer M, Rulicke T, Moser M, Oesch B, McBride PA, Manson JC. Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature, 1996, 380(6575): 639-642
[70] Low MG. The glycosyl-phosphatidylinositol anchor of membrane proteins. Biochim, Biophys Acta, 1989, 988(3): 427-454
[71] Borchelt DR, Rogers M, Stahl N, Telling G, Prusiner SB. Release of the cellular prion protein from cultured cells after loss of its glycoinositol phospholipid anchor. Glycobiology, 1993, 3(4):319-329
[72] Harris DA, Gorodinsky A, Lehmann S, Moulder K, Shyng SL. Cell biology of the prion protein. Curr Top Microbiol Immunol, 1996, 207:77-93
[73] Quaglio E, Chiesa R, Harris DA. Copper converts the cellular prion protein into a protease-resistant species that is distinct from the scrapie isoform. J Biol Chem, 2001, 276(14): 11432-11438
[74] Chiesa R, Piccardo P, Quaglio E, Drisaldi B, Si-Hoe SL, Takao M, Ghetti B, Harris DA. Molecular distinction between pathogenic and infectious properties of the priori protein. J Virol, 2003, 77(13): 7611-7622
[75] Bruce M. Strain typing studies of scrapie and BSE. In Methods in Molecular Medicine: Prion Diseases, 1996, pp. 223-236, Humana Press
[76] Scott M, Foster D, Mirenda C, Serban D, Coufal F, Walchli M, Torchia M, Groth D, Carlson G, DeArmond SJ, Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. Cell, 1989, 59: 847-857
[77] Prusiner SB, Groth D, Serban A, Koehler R, Foster D, Torchia M, Burton D, Yang SL, DeArmond SJ. Ablation of the priori protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies. Proc Natl Acad Sci USA, 1993, 90: 10608-10612
[78] Fischer M, Rulicke T, Raeber A, Sailer A, Moser M, Oesch B, Brandner S, Aguzzi A, Weissmann C. Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO J, 1996, 15: 1255-1264
[79] Lasmezas CI, Deslys JP, Robain O, Jaegly A, Beringue V, Peyrin JM, Fournier JG, Hauw JJ, Rossier J, Dormont D. Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science, 1997, 275: 402-405
[80] Manson JC, Jamieson E, Baybutt H, Tuzi NL, Barron R, McCormell I, Somerville R, Ironside J, Will R, Sy MS, Melton DW, Hope J, Bostock C. A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy. EMBO J, 1999, 18: 6855—6864
[81] Thackray AM, Klein MA, Aguzzi A, Bujdoso R. Chronic subclinical prion disease induced by low dose inoculum. J Virol, 2002, 76: 2510-2517
[82] Telling GC, Parchi P, DeArmond SJ, Cortelli P, Montagna P, Gabizon R, Mastrianni J, Lugaresi E, Gambetti P, and Prusiner SB. Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity. Science, 1996, 274 (5295):2079-82.
[83] Collinge J, Palmer MS, Sidle KC, Hill AF, Gowland I, Meads J, Asante E, Bradley R, Doey LJ, Lantos PL. Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature, 1995, 378: 779-783
[84] Scott MR, Safar J, Telling G, Nguyen O, Groth D, Torchia M, Koehler R, Tremblay P, Walther D, Cohen FE, DeArmond SJ, Prusiner SB. Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice. Proc Natl Acad Sci USA, 1997, 94: 14279-14284
[85] Buschmann A, Pfaff E, Reifenberg K, Muller HM, Groschup MH. Detection of cattle-derived BSE prions using transgenic mice overexpressing bovine PrP~c. Arch Virol, 2000, 16: 75-86
[86] Crozet C, Flamant F, Bencsik A, Aubert D, Samarut J, Baron T. Efficient transmission of two different sheep scrapie isolates in transgenic mice expressing the ovine PrP gene. J Virol, 2001, 75: 5328-5334
[87] Vilotte JL, Soulier S, Essalmani R, Stinnakre MG, Vaiman D, Lepourry L, Da Silva JC, Besnard N, Dawson M, Buscbmann A, Groschup M, Petit S, Madelaine MF, Rakatobe S, Le Dur A, Vilette D, Laude H. Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine PrP. J Virol, 2001, 75: 5977-5984
[88] Telling GC, Scott M, Mastrianni J, Gabizon R, Torchia M, Cohen FE, DeArmond SJ, Prusiner SB. Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell, 1995, 83(1): 79-90
[89] Crozet C, Bencsik A, Flamant F, Lezmi S, Samarut J, Baron T. Florid plaques in ovine PrP transgenic mice infected with an experimental ovine BSE. EMBO Rep, 2001, 2: 952-956
[90] Hill AF, Desbruslais M, Joiner S, Sidle KC, Gowland I, Collinge J, Doey LJ, Lantos P. The same prion strain causes vCJD and BSE. Nature, 1997, 389: 448-450
[91] Scott MR, Will R, Ironside J, Nguyen HO, Tremblay P, DeArmond SJ, Prusiner SB. Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci USA, 1999, 96: 15137-15142
[92] Race R, Chesebro B. Scrapie infectivity found in resistant species. Nature, 1998, 392: 770-777
[93] Race R, Raines A, Raymond GJ, Caughey B, Chesebro B. Long-term subclinical carrier state precedes scrapie replication and adaptation in a resistant species: analogies to Bovine Spongiform Encephalopathy and variant Creutzfeldt-Jakob disease in humans. J Virol, 2001, 75, 10106—10112
[94] Bruce ME, McConnell I, Fraser H, Dickinson AG. The disease characteristics of different strains of scrapie in Sine congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. J Gen Virol, 1991, 72: 595-603
[95] Fraser H. Murine scrapie strains, BSE models and genetics. In Sub-acute Spongiform Encephalopathies, 1991, pp. 131-136, Kluwer Academic Publishers, Brussels
[96] Lloyd SE, Linehan JM, Desbruslais M, Joiner S, Buckell J, Brandner S, Wadsworth JD, Collinge J. Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred mice. J Gen Virol, 2004, 85(8):2471-2478
[97] Lloyd SE, Uphill JB, Targonski PV, Fisher EM, Collinge J. Identification of genetic loci affecting mouse adapted bovine spongiform encephalopathy incubation time in mice. Neurogenetics, 2002, 4(2): 77-81
[98] Muramoto T, Kitamoto T, Tateishi J, Goto I. Successful transmission of Creutzfeldt-Jakob disease from human to mouse verified by prion protein accumulation in mouse brains. Brain Res. 1992, 599 (2): 309-316
[99] Glatzel M, Abela E, Maissen M, Aguzzi A. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Eng J Med, 2003, 349: 1812-1820
[100] Head MW, Ritchie D, Smith N, McLoughlin V, Nailon W, Samad S, Masson S, Bishop M, McCardle L, Ironside JW.. Peripheral tissue involvement in sporadic, iatrogenic, and variant Creutzfeldt-Jakob disease: an immunohistochemical, quantitative, and biochemical study. Am J Pathol, 2004, 164: 143-153
[101] Archer F, Bachelin C, Andreoletti O, Besnard N, Perrot G, Langevin C, Le Dur A, Vilette D, Baron-Van Evercooren A, Vilotte JL, Laude H. Cultured peripheral neuroglial cells are highly permissive to sheep prion infection. J Virol, 2004, 78(1): 482-90
[102] Parchi P, Gambetti P. Human prion diseases. Curt Opin Neurol, 1995, 8(4): 286-93
[103] Rubenstein R, Carp RI, Callahan SM. In vitro replication of scrapie agent in a neuronal model: infection of PC12 cells. J Gen Virol, 1984, 65 (Pt 12): 2191-2198
[104] Schatzl HM, Laszlo L, Holtzman DM, Tatzelt J, DeArmond SJ, Weiner RI, MoNey WC, Prusiner SB. A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis. J Virol, 1997, 71(11): 8821-8831
[105] Brown DR, Clive C, Haswell SJ. Antioxidant activity related to copper binding of native prion protein. J Neurochem, 2001, 76(1): 69-76
[106] Rieger R, Edenhofer F, Lasmezas CI, Weiss S. The human 37-kDa laminin receptor precursor interacts with the priori protein in eukaryotic cells. Nat Med, 1997, 3(12): 1383-8
[107] Forloni G, Angeretti N, Chiesa R, Monzani E, Salmona M, Bugiani O, Tagliavini F. Neurotoxicity ofa prion protein fragment. Nature, 1993, 362(6420): 543-546
[108] Brown DR, Schmidt B, Kretzschmar HA. A priori protein fragment primes type 1 astrocytes to proliferation signals from microglia. Neurobiol Dis, 1998, 4(6): 410-422
[109] Thellung S, Florio T, Corsaro A, Arena S, Merlino M, Salmona M, Tagliavini F, Bugiani O, Forloni G, Schettini G. Apoptotic cell death and impairment of L-type voltage-sensitive calcium channel activity in rat cerebellar granule cells treated with the prion protein fragment 106-126. Neurobiol Dis, 2000, 7(4): 299-309
[110] White AR, Guirguis R, Brazier MW, Jobling MF, Hill AF, Beyreuther K, Barrow CJ, Masters CL, Collins SJ, Cappai R. Sublethal concentrations of prion peptide PrP106-126 or the amyloid beta peptide of Alzheimer's disease activates expression of proapoptotic markers in primary cortical neurons. Neurobiol Dis, 2001, 8(2): 299-316
[111] Bonetto V, Massignan T, Chiesa R, Morbin M, Mazzoleni G, Diomede L, Angeretti N, Colombo L, Forloni G, Tagliavini F, Salmona M. Synthetic miniprion PrP106. J Biol Chem, 2002, 277(35): 31327-32334
[112] Salmona M, Malesani P, De Gioia L, Gorla S, Bruschi M, Molinari A, Della Vedova F, Pedrotti B, Marrari MA, Awan T, Bugiani O, Forloni G, Tagliavini F. Molecular determinants of the physicochemical properties of a critical prion protein region comprising residues 106-126. Biochem J, 1999, 342 (1): 207-214
[113] Ragg E, Tagliavini F, Malesani P, Monticelli L, Bugiani O, Forloni G, Salmona M. Determination of solution conformations of PrP106-126, a neurotoxic fragment of prion protein, by lH NMR and restrained molecular dynamics. Eur J Biochem, 1999, 266(3): 1192-201
[114] Diomede L, Bizzi A, Magistrelli A, Modest EJ, Salmona M, Noseda A. The prion protein and cellular cholesterol homestasis. Neurobiol Lipids, 2002, 3(1): 8-14
[115] Caughey B, Raymond LD, Raymond GJ, Maxson L, Silveira J, Baron GS. Inhibition of protease resistant prion protein accumulation in vitro by curcumin. J Virol, 2003, 77(9):5499-5502
[116] Chung HW. Reverse transcriptase PCR (RT-PCR) and quantitative competitive PCR (QC-PCR). Exp Mol Med, 2001, 33: 85-97
[117] Giulietti A, Overbergh L, Valckx D, Decallonne B, Bouillon R, Mathieu C. An overview of real-time quantitative PCR: application to quantify cytokine gene expression. Methods, 2001, 25(4): 386-401
[118] Heid C A, Stevens J, Livak KJ, Williams PM. Real-time quantitative PCR. Genome Res, 1996, 6 (10): 986-994
[119] Kariyazono H, Ohno T, Thara K, Igarashi H, Joh-o K, Ishikawa S, Hara T. Rapid detection of the 22q11-2 deletion with quantitative real time PCR. Mol Cell Probes, 2001, 15(2): 71-73
[120] Tondella ML, Talkington DF, Holloway BP, Dowell SF, Cowley K, Soriano-Gabarro M, Elkind MS, Fields BS. Development and evaluation of real time PCR based fluorescence assays for detection of Chlamydia pneumonia. J Clin Microbiol, 2002, 40(2): 575-583
[121] Stults JR, Snoeyenbos West O, Methe B, Lovley DR, Chandler DP. Application of the 5' fluorogenic exonuclease assay (Taqman) for quantitative ribosomal DNA and rRNA analysis in sediments. Appl Environ Microbiol, 2001, 67(6): 2781-2789
[122] Matera G, Lamberti A, Quirino A, Foca D, Giancotti A, Barreca GS, Guadagnino V, Liberto MC. Changes in the prevalence of hepatitis C virus(HCV) genotype 4 in Calabria, Southern Italy. Diagn Microbiol Infect Dis, 2002, 42(3):169-173
[123] Helps C, Reeves N, Tasker S, Harbour D. Use of real time quantitative PCR to detect Chlamydophila felis infection. J Clin Microbiol, 2001, 39(7): 2675-2676
[124] Loeffler J, Henke N, Hebart H, Schmidt D, Hagmeyer L, Schumacher U, Einsele H. Quantification of fungal DNA by using fluorescence resonance energy transfer and the light cycler system. J Clin Microbiol, 2000, 38: 586-590
[125] Eckert C, Landt O, Taube T, Seeger K, Beyermann B, Proba J, Henze G. Potential of Lightcycler technology for quantification of minimal residulal disease in childhood acute lymphoblastic leukemia. Leukemia, 2000, 14: 316-323
[126] Kearns AM, Turner AJ, Eltfingham GJ, Freeman R. Rapid detection and quantification of CMV DNA in urine using LightCycler based real-time PCR. J Clin Virol, 2002, 24(1 2): 131-134
[127] Harder TC, Hufnagel M, Zahn K, Beutel K, Schmitt HJ, Ullmann U, Rautenberg P. New Lightcycler PCR for rapid and sensitive quantification of parvovirus B19 DNA guides therapeutic decision making in relapsing infections. J Clin Microbiol, 2001, 39(12): 4413-4419
[128] Bertsch T, Zimmer W, Casarin W, Denz C, Quintel M, Fassbender K. Real-time PCR assay with fluorescent hybridization probes for rapid interleukin 6 promoter genotyping. Clin Chem, 2001, 47: 1873-1874
[129] Yin JL, Shackel NA, Zekry A, McGuinness PH, Richards C, Putten KV, McCaughan GW, Eris JM, Bishop GA. Real time reverse transcriptase polymerase Chain reaction (RT-PCR) for measurement of cytokine and growth factor mRNA expression with fluorogenic probes or SYBRG green I Immunol Cell Biol, 2001, 79(3): 213-221
[130] Lie YS, Petropoulos CJ. Advances in quantitative PCR technology: 5'nuclease assays [J]. Curr Opin Biotechnol, 1998, 9(1): 43-48.
[131] Tyagi S, Bratu DP, Kramer F R. Multicolor molecular beacons for allele discrimination [J]. Nat Biotechnol, 1998, 16(1): 49-53
[132] Whitcombe D, Theaker J, Guy SP, Brown T, Little S. Detection of PCR Products using self-probing amplicons and fluorescence[J]. Nat Biotechnol, 1999, 17(8): 804-807
[133] Becker K, Pan D, Whitely CB. Real-time quantitative polymerase chain reaction to assess gene transfer. Hum Gene Ther, 1999, 10: 2559-2566
[134] Wang X, Li X, Willette RN, Barone FC, Feuerstein GZ. Application of real-time polymerase chain reaction to quantitate induced expression of interleukin-l beta mRNA in ischemic brain tolerance. Neurosci Res, 2000, 59: 238-246
[135] Gibson UE, Heid CA, Williams PM. A novel methods for real time quantitative RT-PCR. Genome Res, 1996, 6: 995-1001
[136] Egawa C, Miyoshi Y, Takamura Y, Taguchi T, Tamaki Y, Noguchi S. Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancer. Int J Cancer, 2001, 95:255-259
[137] Leith CP, Kopecky KJ, Chen IM, Eijdems L, Slovak ML, McConnell TS, Head DR, Weick J, Grever MR, Appelbaum FR, Willman CL. Frequency and clinical significance of the expression of the multidrug resistance proteins MDRl/P glycoprotein, MRPl and LRP in acute myeloid leukemia: a a southwest oncology group study. Blood, 1999, 94(3): 1086-1099
[138] Nuessler V, Stotzer O, Gullis E, Pelka-Fleischer R, Pogrebniak A, Gieseler F, Wilmanns W. Bcl-2, Bax and bcl-xL expression in human sensitive and resistant leukemia cell lines. Leukemia, 1999, 13 (11): 1864-1872
[139] Witham PK Yamashiro CT, Livak KJ, Batt CA. A PCR-based assay for the detection of Escherichia coli Shiga-like toxin genes in ground beef. Appl Environ Microbiol, 1996 62(4): 1347-1353
[140] Chen S, Yee A, Griffiths M, Larkin C, Yamashiro CT, Behari R, Paszko-Kolva C, Rahn K, De Grandis SA. The evaluation of a fluorogenic polymerase chain reaction assay for the detection of Salmonella species in food commodities. Int J Food Microbiol, 1997, 35(3): 239-250
[141] Desjardin LE, Chen Y, Perkins MD, Teixeira L, Cave MD, Eisenach KD. Comparison of the ABI 7700 system (TaqMan) and competitive PCR for quantification of IS6110 DNA in sputum during treatment of tuberculosis. J Clin Microbiol, 1998, 36(7): 1964-1968.
[142] Griscelli F, Barrois M, Chauvin S, Lastere S, Bellet D, Bourhis JH. Quantification of human cytomegalovirus DNA in bone marrow transplant recipients by real-time PCR. J Clin Microbiol, 2001, 39(12): 4362-4369
[143] Walburger DK, Afonina IA, Wydro R. An improved real time PCR method for simultaneous detection of C282Y and H63D mutations in the HFE gene associated with hereditary hemochromatosis. Murat Res, 2001, 15: 121-127
[144] Parks SB, PoPovich BW, Press RD. Real-time polymerase chain reaction with fluorescent hybridization probes for the detection of prevalent mutations causing common thrombophilic and iron overload phenotypes. Am J Clin Pathol, 2001, 115: 439-437
[145] Coasts B, Girodon E, Vidaud D, Flori E, Ardalan A, Conteville P, Fanen P, Niel F, Vidaud M, Goosens M. Prenatal detection by real-time quantitative PCR and characterization of a new CFTR deletion, 3600+15kbde115.3kb (or CFTRdlel9). Clin Chem, 2000, 46: 1417-1420
[146] Lo YM, Lau TK, Zhang J, Leung TN, Chang AM, Hjelm NM, Elmes RS, Bianchi DW. Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21. Clin Chem, 1999, 45: 1745-1751
[147] Paradis V, Laurent A, Flejou JF, Vidaud M, Bedossa P. vidence for the polyclonal nature offocal nodular hyperplasia of the liver by the study of X chromosome inactivation. Hepatology, 1997, 26 (4): 891-895
[148] Dolken L, Schuler F, Dolken G. Quantitative detection of t (14; 18) positive cells by real time quantitative PCR using fluorogenic probes. Biotechniques, 1998, 25(6): 1058-1064
[149] Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, McCardle L, Chree A, Hope J, Birkett C, Cousens S, Fraser H, Bostock CJ. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature, 1997, 389: 498-501
[150] Prusiner S B. Prions. Proc Natl Acta Sci USA, 1998, 95: 13363-13383
[151] Kimberlin RH, Walker CA. Pathogenesis of scrapie (strain 263K) in hamsters infected intracerebrally, intraperitoneally or intraocularly. J Comp Pathol, 1986, 67: 255-263
[152] Aguzzi A, Heppner FL, Heikenwalder M, Prinz M, Mertz K, Seeger H, Glatzel M. Immune system and peripheral nerves in propagation of prions to CNS. Br Med Bull, 2003, 66: 141-159
[153] Terry LA, Marsh S, Ryder SJ, Hawkins SA, Wells GA, Spencer YI. Detection of disease-specific PrP in the distal ileum of cattle exposed orally to the agent of bovine spongiform encephalopathy. Vet Rec, 2003, 152(13): 387-92.
[153] McBride PA, Schulz-Schaeffer WJ, Donaldson M, Bruce ME, Diringer H, Kretzschmar HA, Beekes M. Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves. J Virol, 2001, 75: 9320-9327
[154] Prinz M, Huber G, Macpherson AJ, Heppner FL, Glatzel M, Eugster HP, Wagner N, Aguzzi A. Oral prion infection requires normal numbers of Payer's patches but not of enteric lymphocytes. Am J Pathol, 2003, 162(4): 1103-1111
[155] Prinz M, Heikenwalder M, Junt T, Schwarz P, Glatzel M, Heppner FL, Fu YX, Lipp M, Aguzzi A. Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion. Nature, 2003, 425(6961): 957-962.
[156] Walker N J. Real-time and quantitative PCR: applications to mechanism-based toxicology. J Biochem Mol Toxicol, 2001, 15(3):v121-127.
[157] Seung-I choi, Won-Kyu Ju, Eun-Kyoung Choi Jin Kim. Mitochondrial dysfunction induced by oxidative stress in the brain of hamsters infected with the 263K scrapie agent. Acta Neuropathol, 1998, 96: 279-786.
[158] 孙宪锋,张保云,董小平,等.Scrapie 263K毒株感染金黄地鼠及对其脑组织的组织学研究.病毒学报,2001,16:48-53
[159] 张宝云,侯星生,高晨,等.羊瘙痒病小鼠适应株139A可突破种属屏障颅内感染金黄地鼠.病毒学报,2002,18(4):337-341
[160] 梅英,刘长安,龚建平.定量PCR的研究进展.国外医学临床生物化学与检验学分册,2004,25(1):23-26
[161] van der Velden V H, Hochhaus A, Cazzaniga C. et al. Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: Principles, approaches, and laboratory aspects. Leukemia, 2003, 17(6): 1013-1034
[162] 安靓.医学发育生物学(第一版).北京:人民卫生出版社,2002:101-129
[163] Mehlhom I, Groth D, Stockel J, Moffat B, Reilly D, Yansura D, Willett WS, Baldwin M, Fletterick R, Cohen FE, Vandlen R, Henner D, Prusiner SB. High-level expression and characterization of a purified 142-residue polypeptide of the prion protein. Biochemistry, 1996, 35(17):5528-5537
[164] Hill AF, Antoniou M, Collinge J. Protease-resistant prion protein produced in vitro lacks detectable infectivity. J Gen Virol, 1999, 80 (1): 11-14
[165] Van Everbroeck B, Pals P, Martin JJ, Cras P. Transmissible spongiform encephaiopathies: the story of a pathogenic protein. Peptides, 2002, 23, 1351-1359
[166] Legname G, Baskakov Ⅳ, Nguyen HO, Riesner D, Cohen FE, DeArmond SJ, Prusiner SB. Synthetic mammalian prions. Science, 2004, 305(5684): 673-676
[167] Vorberg I, Priola SA. Molecular basis of scrapie strain glycoform variation. J Biol Chem 2002, 277: 36775-36781
[168] Baskakov Ⅳ, Legname G, Baldwin MA, Prusiner SB, Cohen FE. Pathway complexity of prion protein assembly into amyloid. J. Biol. Chem, 2002, 277(24): 21140-21148
[169] Liu T, Zwingman T, Li R, Pan T, Wong BS, Petersen RB, Gambetti P, Herrup K, Sy MS. Differential expression of cellular prion protein in mouse brain as detected with multiple anti-PrP monoclonal antibodies. Brain Res. 2001, 896(1-2): 118-129.
[170] 鄂征.组织培养和分子细胞学技术.北京出版社,1999
[171] 莫永炎,姜永,陈瑗.大脑星形胶质细胞生物学功能研究进展.生理科学进展,2002,33:71-73
[172] Yang J C, Shan J, Ng K F, et al. Morphine and methadone have different effects on calcium channel currents. Brain Res, 2000, 87(1-2): 199-203
[173] Olliver Milhavet, Sylvain Lehmann. Oxidative stress and the prion protein in transmissible spongiform encephalopathies. Brain Research Review, 2002, 38: 328-339
[174] Isabelle Sponne, Alexandre Fifre, Violette Koziel, et al. Humanin rescues cortical neurons from prion-peptide-induced apoptosis. Mol Cell Neurosci, 2004, 25: 95-102
[175] 王省,蔡新华,孙银平.大鼠小脑皮质颗粒神经元的形态和分布.解剖科学进展,2002,8(3):203-04
[176] Yan GM, Irwin RP, Lin SZ, Weller M, Wood KA, Paul SM. Diphenylhydantoin induces apoptotic cell death of cultured rat cerebellar granule neurons. J Pharmaco Exp Ther, 1995, 274: 983-990
[177] McCarthy KD, Vellis JD. Preparation of separation astroglial and oligdendroglial cell culture from rat cerebral tissue. J Cell Biol, 1980, 85: 890-902
[178] Das GD, Hallas BH, Das KG. Transplantation of brain tissue in the brain of rat, 1. Growth characteristics of neocortical transplants from embryos of different ages. Am J Anat, 1980, 158: 135-145
[179] 忘伯沄,李玉松,黄高昇主编.病理学技术,人民卫生出版社,2001:178-179
[180] 王新亭,徐以明.显示神经元的银浸改良法.解剖学杂志,1994,17(6):557-559
[181] 李文明,苏兴文,邱鹏新等.高钾可以诱导培养的小脑颗粒神经元凋亡.中国神经科学杂志,2001,17(1):88-100
[182] 薛庆善,郭畹华.大鼠大脑皮质星形胶质细胞的体外培养及其促神经突起生长作用研究.神经解剖学杂志,1999,12(2):151-155
[183] Barbin G, Selak I and Manthorpe M. Use of central neuronal cultures for the detection of neuron notrophic agents. Neuroscience, 1984, 12: 33-43
[184] Anderson CNG, Tolkovsky AM. A role for MAPK/ERK in sympathetic neuron survival: protection against a p53-dependent, JNK-independent induction of apoptosis by cytosine arabinoside. J Neurosci, 1999: 664-670
[185] Glub M S, Han B, Keen C L. Aluminum uptake and effects on transferring mediated iron uptake in primary cultures of rat neurons, Astrocytes and oligodendrocytes. Neurotoxicology, 2002, 20(6): 961-970
[186] Benoit Schneider, Vincent Mutel, Mathea Pietri, et al. NADPH oxidase and extracelluar-regulated kinases 1/2 are targets of prion protein signaling in neuronal and nonneuronal cells. PNAS, 2003, 100:13326-13331
[187] Kimelberg H K. Receptors on astrocytes-what possible function? Neurochem Int, 1995, 26(1): 27-40
[188] Prusiner SB. Chemistry and biology of prions. Biochemistry, 1992, 31 (49): 12277-12288.
[189] Collinge J. Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci, 2001, 24: 519-550.
[190] Chiesa R, Harris D A. Prion diseases: what is the neurotoxic molecule? Neurobiol Dis, 2001, 8(5): 743-763
[191] Chen SG, Teplow DB, Parchi P, et al. Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem, 1995, 270(32): 19173-19180.
[192] Florio T, Thellung S, Amico C, et al. Prion protein fragment 106-126 induces apoptotic cell death and impairment of L-type voltage-sensitive calcium channel activity in the GH3 cell line. J Neurosci Res, 1998, 54(3): 341-352
[193] Brown DR, Schmidt B, Kretzschmar H A, Role of microglia and host prion protein in neurotoxicity of a prion protein fragment. Nature, 1996, 380: 345-347
[194] Rymer D L, Good TA. The role of prion peptide structure and aggregation in toxicity and membrane binding. J Neurochem, 2000, 75(6): 2536-2545.
[195] Ettaiche M, Pichot R, Vincent JP, et al. In vivo cytotoxicity of the prion protein fragment 106-126. J Biol Chem, 2000, 275(47): 36487-36490
[196] Brown D R. PrPSc-like prion protein peptide inhibits the function of cellular prion protein. Biochem J, 2000, 352: 511-518.
[197] Lin MC, Mirzabekov T, Kagan BL. Channel formation by a neurotoxic prion protein fragment. J Biol Chem, 1997, 272 (1): 44-47
[198] Manunta M, Kunz B, Sandmeier E, Christen P, Schindler H. Reported channel formation by prion protein fragment 106-126 in planar lipid bilayers cannot be reproduced. FEBS Lett, 2000, 474(2-3): 255-256
[199] Zanata SM, Lopes MH, Mercadante AF, Hajj GN, Chiarini LB, Nomizo R, Freitas AR, Cabral AL, Lee KS, Juliano MA, de Oliveira E, Jachieri SG, Burlingame A, Huang L, Linden R, Brentani RR, Martins VR. Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection. EMBO J, 2002, 21: 3307-3316
[200] Forloni G, Angeretti N, Smiroldo S. Neuroprotective activity of acetyl-L-carnitine: studies in vitro. J Neurosci Res, 1994, 37(1): 92-96
[201] Raeber AJ, Race RE, Brandner S, Priola SA, Sailer A, Bessen RA, Mucke L, Manson J, Aguzzi A, Oldstone MB, Weissmann C, Chesebro B. Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. EMBO J, 1997, 16 (20): 6057-6065
[202] Chabry J, Ratsimanohatra C, Sponne I, Elena PP, Vincent JP, Pillot T. In vivo and in vitro neurotoxicity of the human prion protein (PrP) fragment P118-135 independently of PrP expression. J Neurosci, 2003, 23: 462-469
[203] Diedrich JF, Bendheim PE, Kim YS, Carp RI, Haase AT. Scrapie-associated prion protein accumulates in astrocytes during scrapie infection. Proc Natl Acad Sci USA, 1991, 88(2): 375-379.
[204] Tagliavini F, Forloni G, D'Ursi P, Bugiani O, Salmona M. Studies on peptide fragments of prion proteins. Adv Protein Chem, 2001, 57: 171-201
[205] Shmerling D, Hegyi I, Fischer M, Blattler T, Brandner S, Gotz J, Rulicke T, Flechsig E, Cozzio A, von Mering C, Hangartner C, Aguzzi A, Weissmann C. Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell, 1998, 93: 203-214.
[206] Zahn R, Liu A, Luhrs T, Rick R, von Schroetter C, Lopez Garcia F, Billeter M, Calzolai L, Wider G, Wuthrich K. NMR solution structure of the human prion protein. Proc. Natl Acad Sci USA, 2000, 97(1): 145-150