吉兰—巴雷综合征患者血清的比较蛋白质组学研究
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摘要
目的:吉兰-巴雷综合征(GBS)是一种急性感染性多发性神经病。它是临床上急性迟缓性瘫痪的常见病因之一。以电生理学和神经病理学为依据,吉兰-巴雷综合征有两种主要的类型:急性炎症性脱髓鞘性多发神经病(AIDP)和急性轴索性运动神经病(AMAN)。在北美和欧洲吉兰-巴雷综合征的发病以AIDP为主,神经电生理及神经病理检查示运动神经脱髓鞘而在中国和日本相当多的吉兰-巴雷综合征患者以AMAN发病,神经电生理及神经病理检查示运动神经轴索变性。GBS病因和发病机制尚未完全明确,目前认为它是一种自身免疫性疾病。病原微生物和神经细胞抗原的交叉反应性及抗神经节抗体的存在部分解释了吉兰巴雷综合征的发病机制。而吉兰-巴雷综合征的分子机制尚不明确,目前缺乏有效的可靠的疾病相关的生物学标记。吉兰-巴雷综合征患者血液、脑脊液中存在与发病有关的抗体、补体及细胞因子等,近来以血浆交换疗法及大剂量免疫球蛋白治疗本病,临床证明有效。新近出现的蛋白质组学技术是生命科学进入后基因组时代的标志之一。蛋白质组是指“由一个细胞或组织的基因组所表达的全部相应的蛋白质”。蛋白质是基因功能活动的最终执行者,是生命现象复杂性和多变性的直接体现者,只有从蛋白质组学的角度对所有蛋白质的总和进行研究,才能更加贴近对生命现象和本质的掌握,生命活动的本质和活动规律才能找到答案。蛋白质组学可以比较两个或更多的样品之间的蛋白质水平,是揭示疾病分子机制,发现疾病标志性蛋白,寻找新的药物靶标的理想工具。随着蛋白质组学及其技术在人类疾病和临床医学的应用与发展,“临床蛋白质组学”应运而生。临床蛋白质组学通过对正常个体及病理个体间的蛋白质组比较分析可能找到某些“疾病特异性的蛋白质分子”。血液是取材容易、应用广泛、富含蛋白质的研究样品,其蛋白水平的变化与多种疾病有关。
本研究拟通过对吉兰-巴雷综合征患者与对照者血清的比较蛋白质组学研究,通过定量分析和比较研究在疾病与非疾病状态下蛋白质表达的变化,发现并鉴定疾病过程中的可能蛋白质,探讨吉兰-巴雷综合征的分子学发病机制。
方法:1研究对象:在河北医科大学第二医院就诊的GBS患者(依据Asbury诊断标准)30例和对照者30例的血液样本。2实验步骤:将留取的血液样本离心,取血清置于-80℃冰箱低温保存;去除高丰度蛋白(以bekman公司去除高丰度蛋白试剂盒去除血清中13种高丰度蛋白);对提取的蛋白进行双向凝胶电泳:第一向等电聚焦电泳、第二向垂直SDS-PAGE电泳后、以硝酸银或考马斯亮兰R250显色;透射扫描双向电泳凝胶,所得图谱以ImageMaster 2D Elite软件进行图像分析;将感兴趣蛋白质点从考马斯亮兰染色的凝胶上切下,胶内蛋白质酶解;以MALDI-TOF质谱或MALDI-TOF/TOF串联质谱技术结合数据库检索对蛋白质进行鉴定。
结果:吉兰-巴雷综合征患者与对照者的血清对比,发现14种蛋白及其它们的亚型或前体有显著的改变。其中吉兰-巴雷综合征患者血清中的上调蛋白有11种包括:α1-抗胰凝乳蛋白酶、(肌动蛋白)凝溶胶蛋白亚基前体、非复杂性维生素D结合蛋白晶体结构重链A、补体成分C4B、人类β2-糖蛋白1晶体结构(载脂蛋白H)重链A、血浆铜蓝蛋白、补体C3c重链A、人类补体因子B、人类补体成分C3c重链B、α2-巨球蛋白前体、补体成分1 s亚成分;下调的蛋白有3种包括:纤溶酶原、载脂蛋白E前体、甲状腺素转运蛋白共价二聚体重链A。
结论:目前,关于吉兰-巴雷综合征患者与对照者的血清蛋白质组学研究尚未见报道。此研究结论中的14种蛋白也许与吉兰-巴雷综合征的发病机理相关,它可能为探讨疾病的发病机理提供依据,为疾病的早期诊断提供分子标志,为评价吉兰-巴雷综合征的治疗及预后提供依据。这将为我们今后探讨吉兰-巴雷综合征提供新的研究方向。
Objectives:Guillain-Barrésyndrome (GBS) is an acute inflammatory polyneuropathy . It is now the most common cause of acute flaccid paralysis in the world. Based on electrophysiologic and pathologic findings, GBS has two predominant forms: acute inflammatory demyelinating polyneuro- pathy (AIDP) and acute motor axonal neuropathy (AMAN). In North America and Europe, GBS is usually caused by AIDP, with electrophysiologic evidence of demyelination in both motor and sensory nerve fibers. In contrast, a considerable number of GBS patients have AMAN in China and Japan. The cause and etiopathogenisis of GBS is not completely clear. It is considered to be an autoimmune disease at present. The crossreactivity between microbial and neural antigens partly explains the pathophysiology of the disease and the possible detection of antiganglioside antibodies. However, the molecular mechanisms underlying the disease remain poorly understood and so far no reliable disease-related markers are available. There is antibody, complement and cytokine relative to GBS in the blood and cerebrospinal fluid (CSF) of GBS patients. The immunomodulatory therapy like IVIg or plasmapheresis is proved efficacious. The global analysis of cellular proteins has recently been termed proteomics and is a key area of research that is developing in the post-genome era. Proteomics offers scientists the possibility of identifying disease- associated protein markers to assist in diagnosis or prognosis and to select potential targets for specific drug therapy. Proteomics, the study of identifying the entire protein components (proteome) of a cell, tissue or fluid at agiven point in time.“Clinical proteomics”have appeared following the application and development of proteomics in the human disease and clinical medicine.
Comparative proteomics analysis between normal and abnormal individual may discover some special disease- related protein. We plan to use comparative proteomics to research serum proteins in GBS patients and control subjects which may discover potential proteins about the disease. It may be a way to study the molecular mechanisms of GBS.
Methods:1 Objects: The serum samples from GBS patients ( according to Asbury diagnostic criterion ) and control subjects.All of subjects from the Department of Neurology, the second hospital affiliated Hebei Medical University. 2 Empirical procedures: The blood sample were centrifuged and then stored under -80℃; The rich-abundance protein were removed; The serum proteins extracted with mixture of urea, CHAPS, DTT, IPG buffer and protease inhibitors were run immobilized pH gradient (IPG) isoelectric focusing electrophoresis as the first dimension, and then run vertical SDS-PAGE as the second dimension. The map is visualized by silver staining or colloidal coomassive blue and analysised with ImageMaster 2D Elite software. The proteins of interest were in-gel digested and identified using MALDI-TOF mass spectrometry or MALDI-TOF/TOF tandem mass spectrometry.
Results: Our data showed that the levels of fourteen proteins and their isoforms or their precursor in serum were significantly altered in GBS patients compared with controls.There are fourteen proteins that were up-regulated in serum of GBS patients: alpha-1-antichymotrypsin precursor, gelsolin isoform a precursor, Chain A Crystal Structure Of Uncomplexed Vitamin D-Binding Protein, complement component C4B, Chain A Crystal Structure Of Human Beta-2-Glycoprotein-I (Apolipoprotein-H), ceruloplasmin, Chain A Crig Bound To C3c, Human Complement Factor B, Chain B Human Complement Component C3, Alpha-2-macroglobulin precursor (Alpha-2-M) and complement component 1, s subcomponent. And there are three proteins that were down-regulated: plasminogen, apolipoprotein E precursor, Chain A A Covalent Dimer Of Transthyretin.
Conclusions:Nowadays, there is no report about serologic proteomics analysis between GBS patients and control subjects. We concluded that these fourteen proteins detected from our experiment may be involved in the pathogenesis of GBS. It may provide potential biomarkers for the diagnosis and evaluation of the treatment and prognosis of the disease. It will offer us a new direction to study and research GBS tomorrow.
本研究拟通过对吉兰-巴雷综合征患者与对照者血清的比较蛋白质组学研究,通过定量分析和比较研究在疾病与非疾病状态下蛋白质表达的变化,发现并鉴定疾病过程中的可能蛋白质,探讨吉兰-巴雷综合征的分子学发病机制。
方法:1研究对象:在河北医科大学第二医院就诊的GBS患者(依据Asbury诊断标准)30例和对照者30例的血液样本。2实验步骤:将留取的血液样本离心,取血清置于-80℃冰箱低温保存;去除高丰度蛋白(以bekman公司去除高丰度蛋白试剂盒去除血清中13种高丰度蛋白);对提取的蛋白进行双向凝胶电泳:第一向等电聚焦电泳、第二向垂直SDS-PAGE电泳后、以硝酸银或考马斯亮兰R250显色;透射扫描双向电泳凝胶,所得图谱以ImageMaster 2D Elite软件进行图像分析;将感兴趣蛋白质点从考马斯亮兰染色的凝胶上切下,胶内蛋白质酶解;以MALDI-TOF质谱或MALDI-TOF/TOF串联质谱技术结合数据库检索对蛋白质进行鉴定。
结果:吉兰-巴雷综合征患者与对照者的血清对比,发现14种蛋白及其它们的亚型或前体有显著的改变。其中吉兰-巴雷综合征患者血清中的上调蛋白有11种包括:α1-抗胰凝乳蛋白酶、(肌动蛋白)凝溶胶蛋白亚基前体、非复杂性维生素D结合蛋白晶体结构重链A、补体成分C4B、人类β2-糖蛋白1晶体结构(载脂蛋白H)重链A、血浆铜蓝蛋白、补体C3c重链A、人类补体因子B、人类补体成分C3c重链B、α2-巨球蛋白前体、补体成分1 s亚成分;下调的蛋白有3种包括:纤溶酶原、载脂蛋白E前体、甲状腺素转运蛋白共价二聚体重链A。
结论:目前,关于吉兰-巴雷综合征患者与对照者的血清蛋白质组学研究尚未见报道。此研究结论中的14种蛋白也许与吉兰-巴雷综合征的发病机理相关,它可能为探讨疾病的发病机理提供依据,为疾病的早期诊断提供分子标志,为评价吉兰-巴雷综合征的治疗及预后提供依据。这将为我们今后探讨吉兰-巴雷综合征提供新的研究方向。
Objectives:Guillain-Barrésyndrome (GBS) is an acute inflammatory polyneuropathy . It is now the most common cause of acute flaccid paralysis in the world. Based on electrophysiologic and pathologic findings, GBS has two predominant forms: acute inflammatory demyelinating polyneuro- pathy (AIDP) and acute motor axonal neuropathy (AMAN). In North America and Europe, GBS is usually caused by AIDP, with electrophysiologic evidence of demyelination in both motor and sensory nerve fibers. In contrast, a considerable number of GBS patients have AMAN in China and Japan. The cause and etiopathogenisis of GBS is not completely clear. It is considered to be an autoimmune disease at present. The crossreactivity between microbial and neural antigens partly explains the pathophysiology of the disease and the possible detection of antiganglioside antibodies. However, the molecular mechanisms underlying the disease remain poorly understood and so far no reliable disease-related markers are available. There is antibody, complement and cytokine relative to GBS in the blood and cerebrospinal fluid (CSF) of GBS patients. The immunomodulatory therapy like IVIg or plasmapheresis is proved efficacious. The global analysis of cellular proteins has recently been termed proteomics and is a key area of research that is developing in the post-genome era. Proteomics offers scientists the possibility of identifying disease- associated protein markers to assist in diagnosis or prognosis and to select potential targets for specific drug therapy. Proteomics, the study of identifying the entire protein components (proteome) of a cell, tissue or fluid at agiven point in time.“Clinical proteomics”have appeared following the application and development of proteomics in the human disease and clinical medicine.
Comparative proteomics analysis between normal and abnormal individual may discover some special disease- related protein. We plan to use comparative proteomics to research serum proteins in GBS patients and control subjects which may discover potential proteins about the disease. It may be a way to study the molecular mechanisms of GBS.
Methods:1 Objects: The serum samples from GBS patients ( according to Asbury diagnostic criterion ) and control subjects.All of subjects from the Department of Neurology, the second hospital affiliated Hebei Medical University. 2 Empirical procedures: The blood sample were centrifuged and then stored under -80℃; The rich-abundance protein were removed; The serum proteins extracted with mixture of urea, CHAPS, DTT, IPG buffer and protease inhibitors were run immobilized pH gradient (IPG) isoelectric focusing electrophoresis as the first dimension, and then run vertical SDS-PAGE as the second dimension. The map is visualized by silver staining or colloidal coomassive blue and analysised with ImageMaster 2D Elite software. The proteins of interest were in-gel digested and identified using MALDI-TOF mass spectrometry or MALDI-TOF/TOF tandem mass spectrometry.
Results: Our data showed that the levels of fourteen proteins and their isoforms or their precursor in serum were significantly altered in GBS patients compared with controls.There are fourteen proteins that were up-regulated in serum of GBS patients: alpha-1-antichymotrypsin precursor, gelsolin isoform a precursor, Chain A Crystal Structure Of Uncomplexed Vitamin D-Binding Protein, complement component C4B, Chain A Crystal Structure Of Human Beta-2-Glycoprotein-I (Apolipoprotein-H), ceruloplasmin, Chain A Crig Bound To C3c, Human Complement Factor B, Chain B Human Complement Component C3, Alpha-2-macroglobulin precursor (Alpha-2-M) and complement component 1, s subcomponent. And there are three proteins that were down-regulated: plasminogen, apolipoprotein E precursor, Chain A A Covalent Dimer Of Transthyretin.
Conclusions:Nowadays, there is no report about serologic proteomics analysis between GBS patients and control subjects. We concluded that these fourteen proteins detected from our experiment may be involved in the pathogenesis of GBS. It may provide potential biomarkers for the diagnosis and evaluation of the treatment and prognosis of the disease. It will offer us a new direction to study and research GBS tomorrow.
引文
1 Wasinger VC, Cordwell SJ, Cerpa-Poljak A, et al. Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium. Electrophoresis, 1995, 16(7):1090-1094
2 Beretta L. Proteomics from the clinical perspective: many hopes and much debate. Nat Methods, 2007, 4(10): 785-786
3 G?rg A, Obermaier C, Boguth G, et al. The current state of two-dimensional electrophoresis with immobilized PH gradients. Electrophoresis, 2000, 21(6):1037-1053
4 Heidtmann HH, Nettelbeck DM, Mingels A, et al. Generation of angiostatin-like fragments from plasminogen by prostate- specific antigen. Br J Cancer, 1999, 81(8): 1269-1273
5 Schmitz V, Raskopf E, Gonzalez-Carmona MA, et al. Plasmino- gen derivatives encoding kringles 1-4 and kringles 1-5 exert indirect antiangiogenic and direct antitumoral effects in experimental lung cancer. Cancer Invest, 2008, 26(5): 464-470
6 Raskopf E, Gerceker S, Vogt A,et al. Plasminogen fragment K1-3 inhibits expression of adhesion molecules andexperimental HCC recurrence in the liver. Int J Colorectal Dis, 2009 Jan 27
7 Okada K, Ueshima S, Kawao N, et al. Binding of plasminogen to hepatocytes isolated from injured mouse liver and nonparenchymal-cell-dependent proliferation of hepatocytes. Blood Coagul Fibrinolysis, 2008, 19(6): 503-511
8 Mahley RW, Rall SC Jr. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet, 2000, 1:507-537
9 Adibhatla RM,Hatcher JF. Altered lipid metabolism in brain injury and disorders. Subcell Biochem, 2008, 49: 241-268
10 Marcourakis T, Bahia VS , Kawamoto EM, et al. Apolipoprotein E genotype is related to nitric oxide production in platelets. Cell Biochem Funct, 2008, 26(8): 852-858
11 Lehmensiek V, Süssmuth SD, Tauscher G, et al. Cerebrospinal fluid proteome profile in multiple sclerosis. Mult Scler, 2007, 13(7):840-849
12 Jin T, Hu LS, Chang M, et al. Proteomic identification of potential protein markers in cerebrospinal fluid of GBS patients. Eur J Neurol, 2007, 14(5):563-568
13 Hansson SF, Puchades M, Blennow K, et al. Validation of a prefractionation method followed by two-dimensional electrophoresis - Applied to cerebrospinal fluid proteins from frontotemporal dementia patients. Proteome Sci, 2004, 2(1):7
14 Ando Y, Jono H. Pathogenesis and therapy for transthyretin related amyloidosis. Rinsho Byori, 2008, 56(2):114-120
15 Sekijima Y, Kelly JW, Ikeda S. Pathogenesis of and therapeutic strategies to ameliorate the transthyretin amyloidoses. Curr Pharm Des, 2008, 14(30):3219-3230
16 Naishiro Y,Suzuki C, Kimura M, et al. Plasma analysis of rheumatoid arthritis by SELDI. Nihon Rinsho Meneki Gakkai Kaishi, 2007, 30(3):145-150
17 Chatterji B, Borlak J. A 2-DE MALDI-TOF study to identify disease regulated serum proteins in lung cancer of c-myc transgenic mice. Proteomics, 2009 Jan 29
18 Liz MA, Fleming CE. Substrate specificity of transthyretin: I dentification of natural substrates in the nervous system. Biochem J, 2009 Jan 12
19 Nilsson LN, Bales KR, DiCarlo G, et al. Alpha-1-antichymotrypsin promotes beta-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer's disease. J Neurosci, 2001, 21(5):1444-1451
20 Abraham CR. Reactive astrocytes and alpha1- antichymotrypsin in Alzheimer's disease. Neurobiol Aging, 2001, 22(6):931-936
21 Nielsen HM, Minthon L, Blennow K, et al. Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies. Neurology, 2007, 69(16):1569-1579
22 Li X, Miyajima M, Mineki R,et al. Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathicnormal pressure hydrocephalus by proteomics. Acta Neurochir (Wien), 2006, 148(8):859-864
23 Allen PG. Functional consequences of disulfide bond formation in gelsolin. FEBS Lett, 1997, 401(1):89-94
24 Chauhan V, Ji L, Chauhan A. Anti-amyloidogenic, anti-oxidant and anti-apoptotic role of gelsolin in Alzheimer's disease. Biogerontology, 2008, 9(6):381-389
25 Gay F, Estornes Y, Saurin JC, et al. In colon carcinogenesis, the cytoskeletal protein gelsolin is down-regulated during the transition from adenoma to carcinoma. Hum Pathol, 2008, 39(10):1420-1430
26 Shen JN, Jin S ,Wang J, et al. Detection of serum biomakers of osteosarcoma by proteomic profiling. Zhonghua Zhong Liu Za Zhi, 2008, 30(7): 519-522
27 Speeckaert M, Huang G, Delanghe JR, et al. Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clin Chim Acta, 2006, 372(1-2):33-42
28 Niino M, Fukazawa T, Kikuchi S, et al. Therapeutic Potential of Vitamin D for Multiple Sclerosis. Curr Med Chem, 2008, 15(5):499-505
29 Qin Z, Qin Y, Liu S. Alteration of DBP levels in CSF of patients with MS by proteomics analysis. Cell Mol Neurobiol, 2009, 29(2):203-210
30 Palma AS, De Carvalho M, Grammel N, et al. Proteomic analysis of plasma from Portuguese patients with familialamyotrophic lateral sclerosis. Amyotroph Lateral Scler, 2008 , 9(6):339-349
31 Schwarzenbacher R, Zeth K, Diederichs K, et al. Crystal structure of human beta2-glycoprotein I: implications for phospholipid binding and the antiphospholipid syndrome. EMBO J, 1999, 18(22):6228-6239
32 Bu C, Gao L, Xie W, et al. beta2-glycoprotein I is a cofactor for tissue plasminogen activator-mediated plasminogen activation. Arthritis Rheum, 2009, 60(2): 559-568
33 Musia? J. Beta2 glycoprotein-I the main antigen in antiphospholipid syndrome. Pol Arch Med Wewn, 2007, 117 Suppl:59-60
34 Kaneko K, Hineno A, Yoshida K, et al. Increased vulnerability to rotenone-induced neurotoxicity in ceruloplasmin-deficient mice. Neurosci Lett, 2008, 446(1): 56-58
35 Jursa T, Smith DR. Ceruloplasmin alters the tissue disposition and neurotoxicity of manganese, but not its loading onto transferrin. Toxicol Sci, 2009, 107(1): 182-193
36 Rathore KI, Kerr BJ, Redensek A, et al. Ceruloplasmin protects injured spinal cord from iron-mediated oxidative damage. J Neurosci, 2008, 28(48):12736-12747
37 Uhlikova E, Kupcova V, et al. Plasma copper and ceruloplasmin in patients with alcoholic liver steatosis. Bratisl Lek Listy, 2008, 109(10):431-433
38 Squitti R, Quattrocchi CC, Salustri C, et al. Ceruloplasmin fragmentation is implicated in 'free' copper deregulation of Alzheimer's disease. Prion, 2008, 2(1):23-27
39 Squitti R, Bressi F, Pasqualetti P, et al. Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease. Neurology, 2009, 72(1):50-55
40 Brettschneider J, Mogel H, Lehmensiek V, et al. Proteome analysis of cerebrospinal fluid in amyotrophic lateral sclerosis (ALS). Neurochem Res, 2008, 33(11): 2358-2363
41 Ikai A, Ookata K, Shimizu M, et al. A recombinant bait region mutant of human alpha2-macroglobulin exhibiting an altered proteinase-inhibiting spectrum. Cytotechnology, 1999 , 31(1-2):53-60
42 Yerbury JJ, Kumita JR, Meehan S, et al. alpha2- Macroglobulin and haptoglobin suppress amyloid formation by interacting with prefibrillar protein species.J Biol Chem, 2009, 284(7):4246-4254
43 Poduslo SE, Shook B, Drigalenko E, et al . Lack of association of the two polymerphisms in alpha2 - macroglobulin with Alzheimer disease. Am J Med Genet, 2002, 110(1):30-35
44 RugsarashW, Tungtrongchitr R, Petmitr S, et al . The genetic association between alpha2-macroglobulin (A2M ) gene deletion polymorphism and low serum A2M concentration in over- weight /obese Thais. Nutr Neurosci, 2006, 9(1-2):93-98
45 Thambisetty M, Hye A, Foy C, et al. Proteome-based identification of plasma proteins associated with hippocampal metabolism in early Alzheimer's disease. J Neurol, 2008, 255(11):1712-1720
46 Tanskanen M, Peuralinna T, Polvikoski T, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med, 2008, 40(3):232-239
47 Lin VK, Wang SY, Boetticher NC, et al. Alpha(2)- macroglobulin, a PSA binding protein, is expressed in human prostate stroma. Prostate, 2005, 63(3):299-308
48 Chousa M, Ito H, Saito K, et al. The measurement of serum ceruloplasmin is useful for diagnostic differentiation of immune thrombocytopenic purpura. Clin Chim Acta, 2008, 389 (1-2):132-138
49 Hess D, Schaller J, Rickli EE. Identification of the disulfide bonds of human complement C1s. Biochemistry, 1991, 30(11):2827-2833
50 Kerr FK, O'Brien G, Quinsey NS, et al. Elucidation of the substrate specificity of the C1s protease of the classical complement pathway. J Biol Chem, 2005, 280(47): 39510-39514
51 Illy C, Thielens NM, Gagnon J, et al. Effect of lactoperoxidase-catalyzed iodination on the Ca(2+)- dependent interactions of human C1s. Location of theiodination sites. Biochemistry, 1991, 30(29):7135-7141
52 Levin ME, Jin JG, Ji RR, et al. Complement activation in the peripheral nervous system following the spinal nerve ligation model of neuropathic pain. Pain, 2008, 137(1):182-201
53 Xu Y, Narayana SV, Volanakis JE. Structural biology of the alternative pathway convertase. Immunol Rev, 2001, 180: 123-135
54 Sim RB, Tsiftsoglou SA. Proteases of the complement system. Biochem Soc Trans, 2004, 32(Pt 1):21-27
55 Mollnes TE, Kirschfink M. Strategies of therapeutic complement inhibition. Mol Immunol, 2006, 43(1-2): 107-121
56 Thurman JM, Holers VM. The central role of the alternative complement pathway in human disease.J Immunol, 2006, 176(3):1305-1310
57 A?vazian VA, Boiadzhian AS, Manukian LA, et al. Complement componenets, C3 and factors B, in the blood of patients with acute ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova, 2005, Suppl 15:57-60
58 Rawal N, Rajagopalan R, Salvi VP. Activation of complement component C5: comparison of C5 convertases of the lectin pathway and the classical pathway of complement. J Biol Chem, 2008, 283(12): 7853-7863
59 Giasuddin AS, ElMahdawi JM, ElHassadi FM. Serum complement (C3, C4) levels in patients with acute myocardial infarction and angina pectoris. Bangladesh MedRes Counc Bull, 2007, 33(3):98-102
60 Brueggemann A, Noltze A, Lange T, et al. Significant [C3a] increase in free flaps after prolonged ischemia. J Surg Res, 2008, 150(1):125-130
61 Villiers CL, Cretin F, Lefebvre N, et al. A new role for complement C3: regulation of antigen processing through an inhibitory activity. Mol Immunol, 2008, 45(13): 3509-3516
62 Tüzün E, Li J, Saini SS, et al. Targeting classical complement pathway to treat complement mediated autoimmune diseases. Adv Exp Med Biol, 2008, 632: 265-272
1 Woltjer RL, Cimino PJ, BouttéAM, et al. Proteomic determination of widespread detergent-insolubility including Abeta but not tau early in the pathogenesis of Alzheimer's disease. FASEB J, 2005, 19(13):1923-1925
2 Zhang J, Sokal I,Peskind ER, et al. CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases. Am J Clin Pathol, 2008, 129(4):526-529
3 Finehout EJ, Franck Z, Choe LH, et al. Cerebrospinal fluid proteomic biomarkers for Alzheimer's disease. Ann Neurol, 2007, 61(2):120-129
4 Reed TT, Pierce WM Jr, Turner DM, et al. Proteomic identification of nitrated brain proteins in early Alzheimer's disease inferior parietal lobule. J cell Mol Med, 2008 Aug 21
5 Reed T, Perluigi M, Sultana R, et al. Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease. Neurobiol Dis, 2008, 30(1):107-120
6 Sultana R, Poon HF, Cai J, et al. Identification of nitrated proteins in Alzheimer’s disease brain using a redox proteomics approach. Neurobiol Dis, 2006, 22(1):76-87
7 Sultana R, Boyd-Kimball D, Poon HF, et al. Oxidativemodification and down-regulation of Pin1 in Alzheimer’s disease hippocampus: A redox proteomics analysis. Neurobiol Aging, 2006, 27(7):918-925
8 Choi J, Malakowsky CA, Talent JM, et al. Identification of oxidized plasma proteins in Alzheimer's disease . Biochem Biophys Res Commun, 2002, 293(5):1566-1570
9 Kim HG, Kim KL. Decreased hippocampal cholinergic neurostimulating peptide precursor protein associated with stress exposure in rat brain by proteomic analysis. J Neurosci Res, 2007, 85 (13):2898-2908
10 Hye A, Lynham S, Thambisetty M, et al. Proteome-based plasma biomarkers for Alzheimer’s disease. Brain, 2006, 129(Pt 11):3042-3050
11 Liu HC, Hu CJ, Chang JG, et al. Proteomic identification of lower apolipoprotein A-1 in Alzheimer's disease. Dement Geriatr Cogn Disord, 2006, 21(3):155-161
12 Britschgi M, Wyss-Coray T. Blood Protein Signature for the Early Diagnosis of Alzheimer Disease. Arch Neurol, 2009, 66(2):161-165
13 Sergeant N, Bombois S, Ghestem A, et al. Truncated beta- amyloid peptide species in pre-clinical Alzheimer’s disease as new targets for the vaccination approach. J Neurochem, 2003, 85(6):1581-1591
14 Nilsen J, Irwin Rw, Gallaher TK, et al. Estradiol in vivo regulation of brain mitochondrial proteome. J Neurosci, 2007, 27(51):14069-14077
15 Dhodda VK, Sailor KA, Bowen KK, et al. Putative endogenous mediators of preconditioning - induced ischemic tolerance in rat brain identified by genomic and proteomic analysis. J Neurochem, 2004, 89(1):73-89
16 Junker H, Suofu Y, Venz S, et al. Proteomic identification of an upregulated isoform of annexin A3 in the rat brain following reversible cerebral ischemia. Glia, 2007, 55(16): 1630-1637
17 Zhou Y, Bhatia I, Cai Z, et al. Proteomic analysis of neonatal mouse brain: evidence for hypoxia- and ischemia-induced dephosphorylation of collapsin response mediator proteins. J Proteome Res, 2008, 7(6):2507-2515
18 Zhang X, Guo T, Wang H, et al. Potential biomarkers of acute cerebral infarction detected by SELDI-TOF-MS. Am J Clin Pathol, 2008, 130(2):299-304
19 Jin T, Hu LS, Chang M, et al.Proteomic identification of potential protein markers in cerebrospinal fluid of GBS patients. Eur J Neurol, 2007, 14(5):563-568
20 Lehmensiek V, Süssmuth SD, Brettschneider J, et al. Proteome analysis of cerebrospinal fluid in Guillain-Barrésyndrome (GBS). J Neuroimmunol, 2007, 185(1-2): 190-194
21 Yang YR, Liu SL, Qin ZY, et al. Comparative proteomics analysis of cerebrospinal fluid of patients with Guillain-Barrésyndrome. Cell Mol Neurobiol, 2008, 28(5): 737-744
22 Tian XY, Zhang JZ, Li CY, et al.Preliminary analysis on theproteomic feature of Guillain-Barrésyndrome- associated Campylobacter jejuni. Zhonghua Liu Xing Bing Xue Za Zhi, 2004, 25(3):240-244
23 Lehmensiek V, Süssmuth SD, Tauscher G, et al. Cerebrospinal fluid proteome profile in multiple sclerosis. Mult Scler, 2007, 13(7):840-849
24 Stoop MP, Dekker LJ, Titulaer MK, et al. Multiple sclerosis-related proteins identified in cerebrospinal fluid by advanced mass spectrometry. Proteomics, 2008, 8(8): 1576-1585
25 Chiasserini D, Di Filippo M, Candeliere A, et al. CSF proteome analysis in multiple sclerosis patients by two-dimensional electrophoresis. Eur J Neurol, 2008, 15(9): 998-1001
26 Qin Z, Qin Y, Liu S. Alteration of DBP levels in CSF of patients with MS by proteomics analysis. Cell Mol Neurobiol, 2009, 29(2):203-210
27 Han MH, Hwang SI, Roy DB, et al. Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature, 2008, 451 (7182):1076-1081
28 Yang JW, Czech T, Felizardo M, et al. Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy. Amino Acids, 2006, 30(4): 477-493
29 Jiang W, Du B, Chi Z, et al. Preliminary explorations of the role of mitochondrial proteins in refractory epilepsy: somefindings from comparative proteomics. J Neurosci Res, 2007, 85(14):3160-3170
2 Beretta L. Proteomics from the clinical perspective: many hopes and much debate. Nat Methods, 2007, 4(10): 785-786
3 G?rg A, Obermaier C, Boguth G, et al. The current state of two-dimensional electrophoresis with immobilized PH gradients. Electrophoresis, 2000, 21(6):1037-1053
4 Heidtmann HH, Nettelbeck DM, Mingels A, et al. Generation of angiostatin-like fragments from plasminogen by prostate- specific antigen. Br J Cancer, 1999, 81(8): 1269-1273
5 Schmitz V, Raskopf E, Gonzalez-Carmona MA, et al. Plasmino- gen derivatives encoding kringles 1-4 and kringles 1-5 exert indirect antiangiogenic and direct antitumoral effects in experimental lung cancer. Cancer Invest, 2008, 26(5): 464-470
6 Raskopf E, Gerceker S, Vogt A,et al. Plasminogen fragment K1-3 inhibits expression of adhesion molecules andexperimental HCC recurrence in the liver. Int J Colorectal Dis, 2009 Jan 27
7 Okada K, Ueshima S, Kawao N, et al. Binding of plasminogen to hepatocytes isolated from injured mouse liver and nonparenchymal-cell-dependent proliferation of hepatocytes. Blood Coagul Fibrinolysis, 2008, 19(6): 503-511
8 Mahley RW, Rall SC Jr. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet, 2000, 1:507-537
9 Adibhatla RM,Hatcher JF. Altered lipid metabolism in brain injury and disorders. Subcell Biochem, 2008, 49: 241-268
10 Marcourakis T, Bahia VS , Kawamoto EM, et al. Apolipoprotein E genotype is related to nitric oxide production in platelets. Cell Biochem Funct, 2008, 26(8): 852-858
11 Lehmensiek V, Süssmuth SD, Tauscher G, et al. Cerebrospinal fluid proteome profile in multiple sclerosis. Mult Scler, 2007, 13(7):840-849
12 Jin T, Hu LS, Chang M, et al. Proteomic identification of potential protein markers in cerebrospinal fluid of GBS patients. Eur J Neurol, 2007, 14(5):563-568
13 Hansson SF, Puchades M, Blennow K, et al. Validation of a prefractionation method followed by two-dimensional electrophoresis - Applied to cerebrospinal fluid proteins from frontotemporal dementia patients. Proteome Sci, 2004, 2(1):7
14 Ando Y, Jono H. Pathogenesis and therapy for transthyretin related amyloidosis. Rinsho Byori, 2008, 56(2):114-120
15 Sekijima Y, Kelly JW, Ikeda S. Pathogenesis of and therapeutic strategies to ameliorate the transthyretin amyloidoses. Curr Pharm Des, 2008, 14(30):3219-3230
16 Naishiro Y,Suzuki C, Kimura M, et al. Plasma analysis of rheumatoid arthritis by SELDI. Nihon Rinsho Meneki Gakkai Kaishi, 2007, 30(3):145-150
17 Chatterji B, Borlak J. A 2-DE MALDI-TOF study to identify disease regulated serum proteins in lung cancer of c-myc transgenic mice. Proteomics, 2009 Jan 29
18 Liz MA, Fleming CE. Substrate specificity of transthyretin: I dentification of natural substrates in the nervous system. Biochem J, 2009 Jan 12
19 Nilsson LN, Bales KR, DiCarlo G, et al. Alpha-1-antichymotrypsin promotes beta-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer's disease. J Neurosci, 2001, 21(5):1444-1451
20 Abraham CR. Reactive astrocytes and alpha1- antichymotrypsin in Alzheimer's disease. Neurobiol Aging, 2001, 22(6):931-936
21 Nielsen HM, Minthon L, Blennow K, et al. Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies. Neurology, 2007, 69(16):1569-1579
22 Li X, Miyajima M, Mineki R,et al. Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathicnormal pressure hydrocephalus by proteomics. Acta Neurochir (Wien), 2006, 148(8):859-864
23 Allen PG. Functional consequences of disulfide bond formation in gelsolin. FEBS Lett, 1997, 401(1):89-94
24 Chauhan V, Ji L, Chauhan A. Anti-amyloidogenic, anti-oxidant and anti-apoptotic role of gelsolin in Alzheimer's disease. Biogerontology, 2008, 9(6):381-389
25 Gay F, Estornes Y, Saurin JC, et al. In colon carcinogenesis, the cytoskeletal protein gelsolin is down-regulated during the transition from adenoma to carcinoma. Hum Pathol, 2008, 39(10):1420-1430
26 Shen JN, Jin S ,Wang J, et al. Detection of serum biomakers of osteosarcoma by proteomic profiling. Zhonghua Zhong Liu Za Zhi, 2008, 30(7): 519-522
27 Speeckaert M, Huang G, Delanghe JR, et al. Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clin Chim Acta, 2006, 372(1-2):33-42
28 Niino M, Fukazawa T, Kikuchi S, et al. Therapeutic Potential of Vitamin D for Multiple Sclerosis. Curr Med Chem, 2008, 15(5):499-505
29 Qin Z, Qin Y, Liu S. Alteration of DBP levels in CSF of patients with MS by proteomics analysis. Cell Mol Neurobiol, 2009, 29(2):203-210
30 Palma AS, De Carvalho M, Grammel N, et al. Proteomic analysis of plasma from Portuguese patients with familialamyotrophic lateral sclerosis. Amyotroph Lateral Scler, 2008 , 9(6):339-349
31 Schwarzenbacher R, Zeth K, Diederichs K, et al. Crystal structure of human beta2-glycoprotein I: implications for phospholipid binding and the antiphospholipid syndrome. EMBO J, 1999, 18(22):6228-6239
32 Bu C, Gao L, Xie W, et al. beta2-glycoprotein I is a cofactor for tissue plasminogen activator-mediated plasminogen activation. Arthritis Rheum, 2009, 60(2): 559-568
33 Musia? J. Beta2 glycoprotein-I the main antigen in antiphospholipid syndrome. Pol Arch Med Wewn, 2007, 117 Suppl:59-60
34 Kaneko K, Hineno A, Yoshida K, et al. Increased vulnerability to rotenone-induced neurotoxicity in ceruloplasmin-deficient mice. Neurosci Lett, 2008, 446(1): 56-58
35 Jursa T, Smith DR. Ceruloplasmin alters the tissue disposition and neurotoxicity of manganese, but not its loading onto transferrin. Toxicol Sci, 2009, 107(1): 182-193
36 Rathore KI, Kerr BJ, Redensek A, et al. Ceruloplasmin protects injured spinal cord from iron-mediated oxidative damage. J Neurosci, 2008, 28(48):12736-12747
37 Uhlikova E, Kupcova V, et al. Plasma copper and ceruloplasmin in patients with alcoholic liver steatosis. Bratisl Lek Listy, 2008, 109(10):431-433
38 Squitti R, Quattrocchi CC, Salustri C, et al. Ceruloplasmin fragmentation is implicated in 'free' copper deregulation of Alzheimer's disease. Prion, 2008, 2(1):23-27
39 Squitti R, Bressi F, Pasqualetti P, et al. Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease. Neurology, 2009, 72(1):50-55
40 Brettschneider J, Mogel H, Lehmensiek V, et al. Proteome analysis of cerebrospinal fluid in amyotrophic lateral sclerosis (ALS). Neurochem Res, 2008, 33(11): 2358-2363
41 Ikai A, Ookata K, Shimizu M, et al. A recombinant bait region mutant of human alpha2-macroglobulin exhibiting an altered proteinase-inhibiting spectrum. Cytotechnology, 1999 , 31(1-2):53-60
42 Yerbury JJ, Kumita JR, Meehan S, et al. alpha2- Macroglobulin and haptoglobin suppress amyloid formation by interacting with prefibrillar protein species.J Biol Chem, 2009, 284(7):4246-4254
43 Poduslo SE, Shook B, Drigalenko E, et al . Lack of association of the two polymerphisms in alpha2 - macroglobulin with Alzheimer disease. Am J Med Genet, 2002, 110(1):30-35
44 RugsarashW, Tungtrongchitr R, Petmitr S, et al . The genetic association between alpha2-macroglobulin (A2M ) gene deletion polymorphism and low serum A2M concentration in over- weight /obese Thais. Nutr Neurosci, 2006, 9(1-2):93-98
45 Thambisetty M, Hye A, Foy C, et al. Proteome-based identification of plasma proteins associated with hippocampal metabolism in early Alzheimer's disease. J Neurol, 2008, 255(11):1712-1720
46 Tanskanen M, Peuralinna T, Polvikoski T, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med, 2008, 40(3):232-239
47 Lin VK, Wang SY, Boetticher NC, et al. Alpha(2)- macroglobulin, a PSA binding protein, is expressed in human prostate stroma. Prostate, 2005, 63(3):299-308
48 Chousa M, Ito H, Saito K, et al. The measurement of serum ceruloplasmin is useful for diagnostic differentiation of immune thrombocytopenic purpura. Clin Chim Acta, 2008, 389 (1-2):132-138
49 Hess D, Schaller J, Rickli EE. Identification of the disulfide bonds of human complement C1s. Biochemistry, 1991, 30(11):2827-2833
50 Kerr FK, O'Brien G, Quinsey NS, et al. Elucidation of the substrate specificity of the C1s protease of the classical complement pathway. J Biol Chem, 2005, 280(47): 39510-39514
51 Illy C, Thielens NM, Gagnon J, et al. Effect of lactoperoxidase-catalyzed iodination on the Ca(2+)- dependent interactions of human C1s. Location of theiodination sites. Biochemistry, 1991, 30(29):7135-7141
52 Levin ME, Jin JG, Ji RR, et al. Complement activation in the peripheral nervous system following the spinal nerve ligation model of neuropathic pain. Pain, 2008, 137(1):182-201
53 Xu Y, Narayana SV, Volanakis JE. Structural biology of the alternative pathway convertase. Immunol Rev, 2001, 180: 123-135
54 Sim RB, Tsiftsoglou SA. Proteases of the complement system. Biochem Soc Trans, 2004, 32(Pt 1):21-27
55 Mollnes TE, Kirschfink M. Strategies of therapeutic complement inhibition. Mol Immunol, 2006, 43(1-2): 107-121
56 Thurman JM, Holers VM. The central role of the alternative complement pathway in human disease.J Immunol, 2006, 176(3):1305-1310
57 A?vazian VA, Boiadzhian AS, Manukian LA, et al. Complement componenets, C3 and factors B, in the blood of patients with acute ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova, 2005, Suppl 15:57-60
58 Rawal N, Rajagopalan R, Salvi VP. Activation of complement component C5: comparison of C5 convertases of the lectin pathway and the classical pathway of complement. J Biol Chem, 2008, 283(12): 7853-7863
59 Giasuddin AS, ElMahdawi JM, ElHassadi FM. Serum complement (C3, C4) levels in patients with acute myocardial infarction and angina pectoris. Bangladesh MedRes Counc Bull, 2007, 33(3):98-102
60 Brueggemann A, Noltze A, Lange T, et al. Significant [C3a] increase in free flaps after prolonged ischemia. J Surg Res, 2008, 150(1):125-130
61 Villiers CL, Cretin F, Lefebvre N, et al. A new role for complement C3: regulation of antigen processing through an inhibitory activity. Mol Immunol, 2008, 45(13): 3509-3516
62 Tüzün E, Li J, Saini SS, et al. Targeting classical complement pathway to treat complement mediated autoimmune diseases. Adv Exp Med Biol, 2008, 632: 265-272
1 Woltjer RL, Cimino PJ, BouttéAM, et al. Proteomic determination of widespread detergent-insolubility including Abeta but not tau early in the pathogenesis of Alzheimer's disease. FASEB J, 2005, 19(13):1923-1925
2 Zhang J, Sokal I,Peskind ER, et al. CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases. Am J Clin Pathol, 2008, 129(4):526-529
3 Finehout EJ, Franck Z, Choe LH, et al. Cerebrospinal fluid proteomic biomarkers for Alzheimer's disease. Ann Neurol, 2007, 61(2):120-129
4 Reed TT, Pierce WM Jr, Turner DM, et al. Proteomic identification of nitrated brain proteins in early Alzheimer's disease inferior parietal lobule. J cell Mol Med, 2008 Aug 21
5 Reed T, Perluigi M, Sultana R, et al. Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease. Neurobiol Dis, 2008, 30(1):107-120
6 Sultana R, Poon HF, Cai J, et al. Identification of nitrated proteins in Alzheimer’s disease brain using a redox proteomics approach. Neurobiol Dis, 2006, 22(1):76-87
7 Sultana R, Boyd-Kimball D, Poon HF, et al. Oxidativemodification and down-regulation of Pin1 in Alzheimer’s disease hippocampus: A redox proteomics analysis. Neurobiol Aging, 2006, 27(7):918-925
8 Choi J, Malakowsky CA, Talent JM, et al. Identification of oxidized plasma proteins in Alzheimer's disease . Biochem Biophys Res Commun, 2002, 293(5):1566-1570
9 Kim HG, Kim KL. Decreased hippocampal cholinergic neurostimulating peptide precursor protein associated with stress exposure in rat brain by proteomic analysis. J Neurosci Res, 2007, 85 (13):2898-2908
10 Hye A, Lynham S, Thambisetty M, et al. Proteome-based plasma biomarkers for Alzheimer’s disease. Brain, 2006, 129(Pt 11):3042-3050
11 Liu HC, Hu CJ, Chang JG, et al. Proteomic identification of lower apolipoprotein A-1 in Alzheimer's disease. Dement Geriatr Cogn Disord, 2006, 21(3):155-161
12 Britschgi M, Wyss-Coray T. Blood Protein Signature for the Early Diagnosis of Alzheimer Disease. Arch Neurol, 2009, 66(2):161-165
13 Sergeant N, Bombois S, Ghestem A, et al. Truncated beta- amyloid peptide species in pre-clinical Alzheimer’s disease as new targets for the vaccination approach. J Neurochem, 2003, 85(6):1581-1591
14 Nilsen J, Irwin Rw, Gallaher TK, et al. Estradiol in vivo regulation of brain mitochondrial proteome. J Neurosci, 2007, 27(51):14069-14077
15 Dhodda VK, Sailor KA, Bowen KK, et al. Putative endogenous mediators of preconditioning - induced ischemic tolerance in rat brain identified by genomic and proteomic analysis. J Neurochem, 2004, 89(1):73-89
16 Junker H, Suofu Y, Venz S, et al. Proteomic identification of an upregulated isoform of annexin A3 in the rat brain following reversible cerebral ischemia. Glia, 2007, 55(16): 1630-1637
17 Zhou Y, Bhatia I, Cai Z, et al. Proteomic analysis of neonatal mouse brain: evidence for hypoxia- and ischemia-induced dephosphorylation of collapsin response mediator proteins. J Proteome Res, 2008, 7(6):2507-2515
18 Zhang X, Guo T, Wang H, et al. Potential biomarkers of acute cerebral infarction detected by SELDI-TOF-MS. Am J Clin Pathol, 2008, 130(2):299-304
19 Jin T, Hu LS, Chang M, et al.Proteomic identification of potential protein markers in cerebrospinal fluid of GBS patients. Eur J Neurol, 2007, 14(5):563-568
20 Lehmensiek V, Süssmuth SD, Brettschneider J, et al. Proteome analysis of cerebrospinal fluid in Guillain-Barrésyndrome (GBS). J Neuroimmunol, 2007, 185(1-2): 190-194
21 Yang YR, Liu SL, Qin ZY, et al. Comparative proteomics analysis of cerebrospinal fluid of patients with Guillain-Barrésyndrome. Cell Mol Neurobiol, 2008, 28(5): 737-744
22 Tian XY, Zhang JZ, Li CY, et al.Preliminary analysis on theproteomic feature of Guillain-Barrésyndrome- associated Campylobacter jejuni. Zhonghua Liu Xing Bing Xue Za Zhi, 2004, 25(3):240-244
23 Lehmensiek V, Süssmuth SD, Tauscher G, et al. Cerebrospinal fluid proteome profile in multiple sclerosis. Mult Scler, 2007, 13(7):840-849
24 Stoop MP, Dekker LJ, Titulaer MK, et al. Multiple sclerosis-related proteins identified in cerebrospinal fluid by advanced mass spectrometry. Proteomics, 2008, 8(8): 1576-1585
25 Chiasserini D, Di Filippo M, Candeliere A, et al. CSF proteome analysis in multiple sclerosis patients by two-dimensional electrophoresis. Eur J Neurol, 2008, 15(9): 998-1001
26 Qin Z, Qin Y, Liu S. Alteration of DBP levels in CSF of patients with MS by proteomics analysis. Cell Mol Neurobiol, 2009, 29(2):203-210
27 Han MH, Hwang SI, Roy DB, et al. Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature, 2008, 451 (7182):1076-1081
28 Yang JW, Czech T, Felizardo M, et al. Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy. Amino Acids, 2006, 30(4): 477-493
29 Jiang W, Du B, Chi Z, et al. Preliminary explorations of the role of mitochondrial proteins in refractory epilepsy: somefindings from comparative proteomics. J Neurosci Res, 2007, 85(14):3160-3170