线粒体融合与分裂在中枢神经系统疾病中的研究进展
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摘要
线粒体是一种高度动态的细胞器,通过不断的融合和分裂维持其动态平衡,参与生理病理功能调节。线粒体融合与分裂主要由融合分裂相关蛋白调控,如Drp1、Fis1、Mfn1、Mfn2、OPA1等,多种诱导因子通过调节线粒体融合分裂相关蛋白表达及活化进而调节线粒体形态和生理功能。现有研究表明线粒体融合分裂的异常可能是许多中枢神经系统疾病的发病机制之一。本文从线粒体融合分裂的分子调控机制及其在缺血性脑中风、帕金森综合征和阿尔兹海默症等中枢神经系统疾病中的研究进展方面进行综述,为相关疾病的防治提供一定参考和线索。
Mitochondria is a highly dynamic organelle with coordinately fusion and fission, which is involved in in the regulation of physiological and pathological functions. The balance of mitochondrial dynamics is regulated by certain related proteins, such as dynamin-related protein 1(Drp1), fission 1(Fis1), mitofusin1(Mfn1), mitofusin2(Mfn2), optic atrophy 1(OPA1), et al. A variety of inducible factors regulate the mitochondrial morphology and physiological functions by modulating the expression and activation of mitochondrial fusion and fission-associated proteins. Increasing evidences show that abnormal mitochondrial dynamics is involved in many central nervous system diseases, such as stroke, Alzheimer's disease, Parkinson's disease and so on, which indicate that unbalance of mitochondrial fission and fusion is one of mechanisms of central nervous system diseases. This paper reviews the current advances of abnormal mitochondrial dynamics relevant to neuronal dysfunction in central nervous system diseases, so as to provide some clues or references for the prevention and treatment of the related diseases.
Mitochondria is a highly dynamic organelle with coordinately fusion and fission, which is involved in in the regulation of physiological and pathological functions. The balance of mitochondrial dynamics is regulated by certain related proteins, such as dynamin-related protein 1(Drp1), fission 1(Fis1), mitofusin1(Mfn1), mitofusin2(Mfn2), optic atrophy 1(OPA1), et al. A variety of inducible factors regulate the mitochondrial morphology and physiological functions by modulating the expression and activation of mitochondrial fusion and fission-associated proteins. Increasing evidences show that abnormal mitochondrial dynamics is involved in many central nervous system diseases, such as stroke, Alzheimer's disease, Parkinson's disease and so on, which indicate that unbalance of mitochondrial fission and fusion is one of mechanisms of central nervous system diseases. This paper reviews the current advances of abnormal mitochondrial dynamics relevant to neuronal dysfunction in central nervous system diseases, so as to provide some clues or references for the prevention and treatment of the related diseases.
引文
[1]Golpich M,Amini E,Mohamed Z,et al.Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases:Pathogenesis and Treatment[J].CNS Neuroscience&Therapeutics,2016,23(11):1-18
[2]CalìT,Ottolini D,Brini M.Mitochondrial Ca(2+)and neurodegeneration[J].Cell Calcium,2012,52(1):73-85
[3]Park J,Choi H,Min JS,et al.Loss of mitofusin 2 links beta-amyloid-mediated mitochondrial fragmentation and Cdk5-induced oxidative stress in neuron cells[J].J Neurochem,2014,132(6):687-702
[4]Misko AL,Sasaki Y,Tuck E,et al.Mitofusin2 mutations disrupt axonal mitochondrial positioning and promote axon degeneration[J].J Neurosci,2012,32(12):4145
[5]Brooks C,Cho SG,Wang CY,et al.Fragmented mitochondria are sensitized to Bax insertion and activation during apoptosis[J].Am J Physiol Cell Physiol,2011,300(3):C447-455
[6]Martin OJ,Lai L,Soundarapandian MM,et al.A role for peroxisome proliferator-activated receptorγcoactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth[J].Circ Res,2014,114(4):626-636
[7]Hernándezalvarez MI,Paz JC,Sebastián D,et al.Glucocorticoid modulation of mitochondrial function in hepatoma cells requires the mitochondrial fission protein Drp1[J].Antioxid Redox Signal,2013,19(4):366-378
[8]Li J,Li Y,Jiao J,et al.Mitofusin 1 is negatively regulated by micro RNA 140 in cardiomyocyte apoptosis[J].Mol Cell Biol,2014,34(10):1788-1799
[9]Lee JY,Kapur M,Li M,et al.MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria[J].J Cell Sci,2014,127(Pt 22):4954-4963
[10]Martorell-Riera A,Segarra-Mondejar M,Muoz JP,et al.Mfn2downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death[J].EMBO J,2014,33(20):2388-2407
[11]Leboucher GP,Tsai YC,Yang M,et al.Stress-Induced Phosphorylation and Proteasomal Degradation of Mitofusin 2 Facilitates Mitochondrial Fragmentation and Apoptosis[J].Mol Cell,2012,47(4):547-557
[12]Chen Y,Nd DG.PINK1-Phosphorylated Mitofusin 2 is a Parkin Receptor for Culling Damaged Mitochondria[J].Science,2013,340(6131):471-475
[13]Yue W,Chen Z,Liu H,et al.A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30[J].Cell Res,2014,24(4):482-496
[14]Lee H,Smith SB,Yoon Y.The Short Variant of the Mitochondrial Dynamin OPA1 Maintains Mitochondrial Energetics and Cristae Structure[J].J Biol Chem,2017,292(17):7115-7130
[15]Zorzano A,Claret M.Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction[J].Front Aging Neurosci,2015,7:101
[16]Toda C,Kim JD,Impellizzeri D,et al.UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness[J].Cell,2016,164(5):872-883
[17]Kiely AP,Moloney AM,O'Flanagan C,et al.Defects in PINK1 are part of Alzheimer's disease pathogenesis and associate with alterations in the mitochondrial fission protein Drp1[J].Mov Disord,2012,27:S493-S494
[18]Kim DI,Lee KH,Gabr AA,et al.Aβ-Induced Drp1 phosphorylation through Akt activation promotes excessive mitochondrial fission leading to neuronal apoptosis[J].Biochim Biophys Acta,2016,1863(11):2820-2834
[19]Rambold AS,Kostelecky B,Elia N,et al.Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation[J].Proc Natl Acad Sci U S A.2011,108(25):10190-10195
[20]Wang W,Wang Y,Long J,et al.Mitochondrial fission triggered by hyperglycemia is mediated by ROCK1 activation in podocytes and endothelial cells[J].Cell Metab,2012,15(2):186-200
[21]Otera H,Ishihara N,Mihara K.New insights into the function and regulation of mitochondrial fission[J].Biochim Biophys Acta,2013,1833(5):1256-1268
[22]Xu S,Cherok E,Das S,et al.Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of Mi D49 protein[J].Mol Biol Cell,2016,27(2):349-359
[23]Balog J,Mehta SL,Vemuganti R.Mitochondrial fission and fusion in secondary brain damage after CNS insults[J].J Cereb Blood Flow Metab,2016,36(12):2022-2033
[24]Reddy PH,Reddy TP,Manczak M,et al.Dynamin-Related Protein 1and Mitochondrial Fragmentation in Neurodegenerative Diseases[J].Brain Res Rev,2011,67(1-2):103-118
[25]Haun F,Nakamura T,Shiu AD,et al.S-nitrosylation of dynamin-related protein 1 mediates mutant huntingtin-induced mitochondrial fragmentation and neuronal injury in Huntington's disease[J].Antioxid Redox Signal,2013,19(11):1173-1184
[26]Zhang Z,Lei L,Jiang X,et al.The essential role of Drp1 and its regulation by S-nitrosylation of Parkin in dopaminergic neurodegeneration:implications for Parkinson's disease[J].Antioxid Redox Signal,2016,25(11):609-622
[27]Cho DH,Nakamura T,Fang J,et al.S-Nitrosylation of Drp1 Mediatesβ-Amyloid-Related Mitochondrial Fission and Neuronal Injury[J].Science,2009,324(5923):102-105
[28]Gawlowski T,Suarez J,Scott B,et al.Modulation of dynamin-related protein 1(DRP1)function by increased O-linked-β-N-acetylglucosamine modification(O-Glc NAc)in cardiac myocytes[J].J Biol Chem,2012,287(35):30024-30034
[29]Kumar R,Bukowski MJ,Wider JM,et al.Mitochondrial dynamics following global cerebral ischemia[J].Mol Cell Neurosci,2016,76:68-75
[30]Mei C,Ding H,Chen F,et al.Mdivi-1 Protects Against Ischemic Brain Injury via Elevating Extracellular Adenosine in a c AMP/CREB-CD39-Dependent Manner[J].Mol Neurobiol,2016,53(1):240-253
[31]Tang Y,Liu X,Jie Z,et al.Hypothermia-induced Ischemic Tolerance is associated with Drp1 Inhibition in Cerebral Ischemia-reperfusion Injury of Mice[J].Brain Res,2016,1646:73-83
[32]Martorell-Riera A,Segarra-Mondejar M,Mu?oz JP,et al.Mfn2downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death[J].EMBO J,2014,33(20):2388-2407
[33]Wang W,Zhang F,Li L,et al.MFN2 couples glutamate excitotoxicity and mitochondrial dysfunction in motor neurons[J].J Biol Chem,2014,290(1):168-182
[34]Zhao YX,Cui M,Chen SF,et al.Amelioration of ischemic mitochondrial injury and Bax-dependent outer membrane permeabilization by Mdivi-1[J].CNS Neuroscience&Therapeutics,2014,20(6):528-538
[35]Zhang XM,Zhang L,Wang G,et al.Suppression of mitochondrial fission in experimental cerebral ischemia:The potential neuroprotective target of p38 MAPK inhibition[J].Neurochem Int,2015,90:1-8
[36]Zuo W,Zhang S,Xia CY,et al.Mitochondria autophagy is induced after hypoxic/ischemic stress in a Drp1 dependent manner:the role of inhibition of Drp1 in ischemic brain damage[J].Neuropharmacology,2014,86:103-115
[37]Zuo W,Yang PF,Chen J,et al.Drp-1,a potential therapeutic target for brain ischaemic stroke[J].Br J Pharmacol,2016,173(10):1665-1677
[38]Chen SD,Lin TK,Yang DI,et al.Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemiainduced hippocampal neuronal injury[J].Biochem Biophys Res Commun,2015,460(2):397-403
[39]Zhao Y,Chen F,Chen S,et al.The Parkinson's disease-associated gene PINK1 protects neurons from ischemic damage by decreasing mitochondrial translocation of the fission promoter Drp1[J].J Neurochem,2013,127(5):711-722
[40]Kim T,Mehta SL,Kaimal B,et al.Poststroke Induction ofα-Synuclein Mediates Ischemic Brain Damage[J].J Neurosci,2016,36(26):7055-7065
[41]Slupe AM,Merrill RA,Flippo KH,et al.A Calcineurin Docking Motif(LXVP)in Dynamin-related Protein 1 Contributes to Mitochondrial Fragmentation and Ischemic Neuronal Injury[J].J Biol Chem,2013,288(17):12353-12365
[42]Li Z,He Z,Zhang Q,et al.Exercise Pretreatment Promotes Mitochondrial Dynamic Protein OPA1 Expression after Cerebral Ischemia in Rats[J].Int J Mol Sci,2014,15(3):4453-4463
[43]Wang H,Zheng S,Liu M,et al.The Effect of Propofol on Mitochondrial Fission during Oxygen-Glucose Deprivation and Reperfusion Injury in Rat Hippocampal Neurons[J].Plo S one,2016,11(10):e0165052
[44]Manczak M,Calkins MJ,Reddy PH.Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease:implications for neuronal damage[J].Hum Mol Genet,2011,20(13):2495-2509
[45]Yan J,Liu XH,Han MZ,et al.Blockage of GSK3β-mediated Drp1phosphorylation provides neuroprotection in neuronal and mouse models of Alzheimer's disease[J].Neurobiol Aging,2015,36(1):211-227
[46]Manczak M,Reddy PH.Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer's disease neurons:implications for mitochondrial dysfunction and neuronal damage[J].Hum Mol Genet,2012,21(11):2538-2347
[47]Norris KL,Hao R,Chen LF,et al.Convergence of Parkin,PINK1,andα-Synuclein on Stress-induced Mitochondrial Morphological Remodeling[J].J Biol Chem,2015,290(22):13862-13874
[48]Gui YX,Wang XY,Kang WY,et al.Extracellular signal-regulated kinase is involved in alpha-synuclein-induced mitochondrial dynamic disorders by regulating dynamin-like protein 1[J].Neurobiol Aging,2012,33(12):2841-2854
[49]Buhlman L,Damiano M,Bertolin G,et al.Functional interplay between Parkin and Drp1 in mitochondrial fission and clearance[J].Biochim Biophys Acta,2014,1843(9):2012-2026
[50]Rappold PM.Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo[J].Nat Commun,2014,5:5244
[51]Irrcher I,Aleyasin H,Seifert EL,et al.Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics[J].Hum Mol Genet,2010,19(19):3734-3746
[52]Wang X,Petrie TG,Liu Y,et al.Parkinson's disease-associated DJ-1mutations impair mitochondrial dynamics and cause mitochondrial dysfunction[J].J Neurochem,2012,121(5):830-839
[53]Chuang JI,Pan IL,Hsieh CY,et al.Melatonin prevents the dynamin-related protein 1-dependent mitochondrial fission and oxidative insult in the cortical neurons after 1-methyl-4-phenylpyridinium treatment[J].J Pineal Res,2016,61(2):230-240
[54]Cherubini M,Ginés S.Mitochondrial fragmentation in neuronal degeneration:Toward an understanding of HD striatal susceptibility[J].Biochem Biophys Res Commun,2017,483(4):1063-1068
[55]Shirendeb UP,Calkins MJ,Manczak M,et al.Mutant huntingtin's interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington's disease[J].Hum Mol Genet,2012,21(2):406-420
[56]Guo X,Disatnik MH,Monbureau M,et al.Inhibition of mitochondrial fragmentation diminishes Huntington's disease-associated neurodegeneration[J].J Clin Invest,2013,123(12):5371-5388
[57]Cherubini M,Puigdellívol M,Alberch J,et al.Cdk5-mediated mitochondrial fission:A key player in dopaminergic toxicity in Huntington's disease[J].Biochim Biophys Acta,2015,1852(10):2145-2160
[58]Wang W,Li L,Lin WL,et al.The ALS disease-associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons[J].Hum Mol Genet,2013,22(23):4706-4719
[2]CalìT,Ottolini D,Brini M.Mitochondrial Ca(2+)and neurodegeneration[J].Cell Calcium,2012,52(1):73-85
[3]Park J,Choi H,Min JS,et al.Loss of mitofusin 2 links beta-amyloid-mediated mitochondrial fragmentation and Cdk5-induced oxidative stress in neuron cells[J].J Neurochem,2014,132(6):687-702
[4]Misko AL,Sasaki Y,Tuck E,et al.Mitofusin2 mutations disrupt axonal mitochondrial positioning and promote axon degeneration[J].J Neurosci,2012,32(12):4145
[5]Brooks C,Cho SG,Wang CY,et al.Fragmented mitochondria are sensitized to Bax insertion and activation during apoptosis[J].Am J Physiol Cell Physiol,2011,300(3):C447-455
[6]Martin OJ,Lai L,Soundarapandian MM,et al.A role for peroxisome proliferator-activated receptorγcoactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth[J].Circ Res,2014,114(4):626-636
[7]Hernándezalvarez MI,Paz JC,Sebastián D,et al.Glucocorticoid modulation of mitochondrial function in hepatoma cells requires the mitochondrial fission protein Drp1[J].Antioxid Redox Signal,2013,19(4):366-378
[8]Li J,Li Y,Jiao J,et al.Mitofusin 1 is negatively regulated by micro RNA 140 in cardiomyocyte apoptosis[J].Mol Cell Biol,2014,34(10):1788-1799
[9]Lee JY,Kapur M,Li M,et al.MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria[J].J Cell Sci,2014,127(Pt 22):4954-4963
[10]Martorell-Riera A,Segarra-Mondejar M,Muoz JP,et al.Mfn2downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death[J].EMBO J,2014,33(20):2388-2407
[11]Leboucher GP,Tsai YC,Yang M,et al.Stress-Induced Phosphorylation and Proteasomal Degradation of Mitofusin 2 Facilitates Mitochondrial Fragmentation and Apoptosis[J].Mol Cell,2012,47(4):547-557
[12]Chen Y,Nd DG.PINK1-Phosphorylated Mitofusin 2 is a Parkin Receptor for Culling Damaged Mitochondria[J].Science,2013,340(6131):471-475
[13]Yue W,Chen Z,Liu H,et al.A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30[J].Cell Res,2014,24(4):482-496
[14]Lee H,Smith SB,Yoon Y.The Short Variant of the Mitochondrial Dynamin OPA1 Maintains Mitochondrial Energetics and Cristae Structure[J].J Biol Chem,2017,292(17):7115-7130
[15]Zorzano A,Claret M.Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction[J].Front Aging Neurosci,2015,7:101
[16]Toda C,Kim JD,Impellizzeri D,et al.UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness[J].Cell,2016,164(5):872-883
[17]Kiely AP,Moloney AM,O'Flanagan C,et al.Defects in PINK1 are part of Alzheimer's disease pathogenesis and associate with alterations in the mitochondrial fission protein Drp1[J].Mov Disord,2012,27:S493-S494
[18]Kim DI,Lee KH,Gabr AA,et al.Aβ-Induced Drp1 phosphorylation through Akt activation promotes excessive mitochondrial fission leading to neuronal apoptosis[J].Biochim Biophys Acta,2016,1863(11):2820-2834
[19]Rambold AS,Kostelecky B,Elia N,et al.Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation[J].Proc Natl Acad Sci U S A.2011,108(25):10190-10195
[20]Wang W,Wang Y,Long J,et al.Mitochondrial fission triggered by hyperglycemia is mediated by ROCK1 activation in podocytes and endothelial cells[J].Cell Metab,2012,15(2):186-200
[21]Otera H,Ishihara N,Mihara K.New insights into the function and regulation of mitochondrial fission[J].Biochim Biophys Acta,2013,1833(5):1256-1268
[22]Xu S,Cherok E,Das S,et al.Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of Mi D49 protein[J].Mol Biol Cell,2016,27(2):349-359
[23]Balog J,Mehta SL,Vemuganti R.Mitochondrial fission and fusion in secondary brain damage after CNS insults[J].J Cereb Blood Flow Metab,2016,36(12):2022-2033
[24]Reddy PH,Reddy TP,Manczak M,et al.Dynamin-Related Protein 1and Mitochondrial Fragmentation in Neurodegenerative Diseases[J].Brain Res Rev,2011,67(1-2):103-118
[25]Haun F,Nakamura T,Shiu AD,et al.S-nitrosylation of dynamin-related protein 1 mediates mutant huntingtin-induced mitochondrial fragmentation and neuronal injury in Huntington's disease[J].Antioxid Redox Signal,2013,19(11):1173-1184
[26]Zhang Z,Lei L,Jiang X,et al.The essential role of Drp1 and its regulation by S-nitrosylation of Parkin in dopaminergic neurodegeneration:implications for Parkinson's disease[J].Antioxid Redox Signal,2016,25(11):609-622
[27]Cho DH,Nakamura T,Fang J,et al.S-Nitrosylation of Drp1 Mediatesβ-Amyloid-Related Mitochondrial Fission and Neuronal Injury[J].Science,2009,324(5923):102-105
[28]Gawlowski T,Suarez J,Scott B,et al.Modulation of dynamin-related protein 1(DRP1)function by increased O-linked-β-N-acetylglucosamine modification(O-Glc NAc)in cardiac myocytes[J].J Biol Chem,2012,287(35):30024-30034
[29]Kumar R,Bukowski MJ,Wider JM,et al.Mitochondrial dynamics following global cerebral ischemia[J].Mol Cell Neurosci,2016,76:68-75
[30]Mei C,Ding H,Chen F,et al.Mdivi-1 Protects Against Ischemic Brain Injury via Elevating Extracellular Adenosine in a c AMP/CREB-CD39-Dependent Manner[J].Mol Neurobiol,2016,53(1):240-253
[31]Tang Y,Liu X,Jie Z,et al.Hypothermia-induced Ischemic Tolerance is associated with Drp1 Inhibition in Cerebral Ischemia-reperfusion Injury of Mice[J].Brain Res,2016,1646:73-83
[32]Martorell-Riera A,Segarra-Mondejar M,Mu?oz JP,et al.Mfn2downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death[J].EMBO J,2014,33(20):2388-2407
[33]Wang W,Zhang F,Li L,et al.MFN2 couples glutamate excitotoxicity and mitochondrial dysfunction in motor neurons[J].J Biol Chem,2014,290(1):168-182
[34]Zhao YX,Cui M,Chen SF,et al.Amelioration of ischemic mitochondrial injury and Bax-dependent outer membrane permeabilization by Mdivi-1[J].CNS Neuroscience&Therapeutics,2014,20(6):528-538
[35]Zhang XM,Zhang L,Wang G,et al.Suppression of mitochondrial fission in experimental cerebral ischemia:The potential neuroprotective target of p38 MAPK inhibition[J].Neurochem Int,2015,90:1-8
[36]Zuo W,Zhang S,Xia CY,et al.Mitochondria autophagy is induced after hypoxic/ischemic stress in a Drp1 dependent manner:the role of inhibition of Drp1 in ischemic brain damage[J].Neuropharmacology,2014,86:103-115
[37]Zuo W,Yang PF,Chen J,et al.Drp-1,a potential therapeutic target for brain ischaemic stroke[J].Br J Pharmacol,2016,173(10):1665-1677
[38]Chen SD,Lin TK,Yang DI,et al.Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemiainduced hippocampal neuronal injury[J].Biochem Biophys Res Commun,2015,460(2):397-403
[39]Zhao Y,Chen F,Chen S,et al.The Parkinson's disease-associated gene PINK1 protects neurons from ischemic damage by decreasing mitochondrial translocation of the fission promoter Drp1[J].J Neurochem,2013,127(5):711-722
[40]Kim T,Mehta SL,Kaimal B,et al.Poststroke Induction ofα-Synuclein Mediates Ischemic Brain Damage[J].J Neurosci,2016,36(26):7055-7065
[41]Slupe AM,Merrill RA,Flippo KH,et al.A Calcineurin Docking Motif(LXVP)in Dynamin-related Protein 1 Contributes to Mitochondrial Fragmentation and Ischemic Neuronal Injury[J].J Biol Chem,2013,288(17):12353-12365
[42]Li Z,He Z,Zhang Q,et al.Exercise Pretreatment Promotes Mitochondrial Dynamic Protein OPA1 Expression after Cerebral Ischemia in Rats[J].Int J Mol Sci,2014,15(3):4453-4463
[43]Wang H,Zheng S,Liu M,et al.The Effect of Propofol on Mitochondrial Fission during Oxygen-Glucose Deprivation and Reperfusion Injury in Rat Hippocampal Neurons[J].Plo S one,2016,11(10):e0165052
[44]Manczak M,Calkins MJ,Reddy PH.Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease:implications for neuronal damage[J].Hum Mol Genet,2011,20(13):2495-2509
[45]Yan J,Liu XH,Han MZ,et al.Blockage of GSK3β-mediated Drp1phosphorylation provides neuroprotection in neuronal and mouse models of Alzheimer's disease[J].Neurobiol Aging,2015,36(1):211-227
[46]Manczak M,Reddy PH.Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer's disease neurons:implications for mitochondrial dysfunction and neuronal damage[J].Hum Mol Genet,2012,21(11):2538-2347
[47]Norris KL,Hao R,Chen LF,et al.Convergence of Parkin,PINK1,andα-Synuclein on Stress-induced Mitochondrial Morphological Remodeling[J].J Biol Chem,2015,290(22):13862-13874
[48]Gui YX,Wang XY,Kang WY,et al.Extracellular signal-regulated kinase is involved in alpha-synuclein-induced mitochondrial dynamic disorders by regulating dynamin-like protein 1[J].Neurobiol Aging,2012,33(12):2841-2854
[49]Buhlman L,Damiano M,Bertolin G,et al.Functional interplay between Parkin and Drp1 in mitochondrial fission and clearance[J].Biochim Biophys Acta,2014,1843(9):2012-2026
[50]Rappold PM.Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo[J].Nat Commun,2014,5:5244
[51]Irrcher I,Aleyasin H,Seifert EL,et al.Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics[J].Hum Mol Genet,2010,19(19):3734-3746
[52]Wang X,Petrie TG,Liu Y,et al.Parkinson's disease-associated DJ-1mutations impair mitochondrial dynamics and cause mitochondrial dysfunction[J].J Neurochem,2012,121(5):830-839
[53]Chuang JI,Pan IL,Hsieh CY,et al.Melatonin prevents the dynamin-related protein 1-dependent mitochondrial fission and oxidative insult in the cortical neurons after 1-methyl-4-phenylpyridinium treatment[J].J Pineal Res,2016,61(2):230-240
[54]Cherubini M,Ginés S.Mitochondrial fragmentation in neuronal degeneration:Toward an understanding of HD striatal susceptibility[J].Biochem Biophys Res Commun,2017,483(4):1063-1068
[55]Shirendeb UP,Calkins MJ,Manczak M,et al.Mutant huntingtin's interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington's disease[J].Hum Mol Genet,2012,21(2):406-420
[56]Guo X,Disatnik MH,Monbureau M,et al.Inhibition of mitochondrial fragmentation diminishes Huntington's disease-associated neurodegeneration[J].J Clin Invest,2013,123(12):5371-5388
[57]Cherubini M,Puigdellívol M,Alberch J,et al.Cdk5-mediated mitochondrial fission:A key player in dopaminergic toxicity in Huntington's disease[J].Biochim Biophys Acta,2015,1852(10):2145-2160
[58]Wang W,Li L,Lin WL,et al.The ALS disease-associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons[J].Hum Mol Genet,2013,22(23):4706-4719
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