tau蛋白过磷酸化与阿尔茨海默病
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摘要
阿尔茨海默病(Alzheimer's disease,AD)是一种神经退行性疾病,为老年痴呆症的主要形式之一。tau蛋白为一种微管相关蛋白,其过度磷酸化在AD的发病过程中起着关键作用。现就近几年关于tau蛋白过度磷酸化的机制、影响因素及其神经毒性作用的最新研究进展作一综述。
Alzheimer's disease(AD) is one kind of neurodegenerative diseases,also the main reason leading to dementia.tau protein is a microtubule-associated protein,and its hyperphosphorylation plays a key role in the pathogenesis of AD.In this review,we made a summary of latest research progresses on the neurotoxicity of tau protein hyperphosphorylation and the relationship between tau protein hyperphosphorylation and AD.
Alzheimer's disease(AD) is one kind of neurodegenerative diseases,also the main reason leading to dementia.tau protein is a microtubule-associated protein,and its hyperphosphorylation plays a key role in the pathogenesis of AD.In this review,we made a summary of latest research progresses on the neurotoxicity of tau protein hyperphosphorylation and the relationship between tau protein hyperphosphorylation and AD.
引文
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[19]Zhou XW,Gustafsson JA,Tanila H,et al.Tau hyperphos-phorylation correlates with reduced methylation of proteinphosphatase 2A.Neurobiol Dis,2008,31(3):386-94
[20]Dai M,Zhang C,Kania U,et al.A PP6-type phosphataseholoenzyme directly regulates PIN phosphorylation andauxin efflux in Arabidopsis.Plant Cell,2012,24(6):2497-514
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[22]Plouffe V,Mohamed NV,Rivest-McGraw J,et al.Hyperphosphorylation and cleavage at D421 enhance tausecretion.PLoS One,2012,7(5):e36873
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[24]Carroll JC,Iba M,Bangasser DA,et al.Chronic stressexacerbates tau pathology,neurodegeneration,andcognitive performance through a corticotropin-releasingfactor receptor-dependent mechanism in a transgenicmouse model of tauopathy.J Neurosci,2011,31(40):14436-49
[25]LaPointe NE,Morfini G,Pigino G,et al.The aminoterminus of tau inhibits kinesin-dependent axonaltransport:implications for filament toxicity.J NeurosciRes,2009,87(2):440-51
[26]Medina DX,Caccamo A,Oddo S.Methylene blue reducesAβlevels and rescues early cognitive deficit by increasingproteasome activity.Brain Pathol,2011,21(2):140-9
[27]Wang Y,Martinez-Vicente M,Kruger U,et al.Taufragmentation,aggregation and clearance:the dual role oflysosomal processing.Hum Mol Genet,2009,18(21):4153-70
[28]Luo W,Dou F,Rodina A,et al.Roles of heat-shockprotein 90 in maintaining and facilitating the neurode-generative phenotype in tauopathies.Proc Natl Acad SciUSA,2007,104(22):9511-6
[29]Funderburk SF,Marcellino BK,Yue Z.Cell"self-eating"(autophagy)mechanism in Alzheimer's disease.Mt Sinai JMed,2010,77(1):59-68
[30]Hung SY,Huang WP,Liou HC,et al.Autophagy protectsneuron from Aβ-induced cytotoxicity.Autophagy,2009,5(4):502-10
[31]Ling D,Song HJ,Garza D,et al.Aβ42-induced neurode-generation via an age-dependent autophagic-lysosomalinjury in Drosophila.PLoS One,2009,4(1):e4201
[2]Yeh PA,Chang CJ,Tu PH,et al.Phosphorylation alterstau distribution and elongates life span in Drosophila.JAlzheimers Dis,2010,21(2):543-56
[3]Hanger DP,Anderton BH,Noble W.Tau phosphorylation:the therapeutic challenge for neurodegenerative disease.Trends Mol Med,2009,15(3):112-9
[4]de Calignon A,Fox LM,Pitstick R,et al.Caspase activationprecedes and leads to tangles.Nature,2010,464(7292):1201-4
[5]Liu F,Liang Z,Shi J,et al.PKA modulates GSK-3β-andcdk5-catalyzed phosphorylation of tau in site-and kinase-specific manners.FEBS Lett,2006,580(26):6269-74
[6]Huang J,Chen YJ,Bian WH,et al.Unilateral amyloid-β25-35injection into the rat amygdala increases the expressionsof aberrant tau phosphorylation kinases.Chin Med J Engl,2010,123(10):1311-4
[7]Qing H,He G,Ly PT,et al.Valproic acid inhibits Aβproduction,neuritic plaque formation,and behavioraldeficits in Alzheimer's disease mouse models.J Exp Med,2008,205(12):2781-9
[8]Gong EJ,Park HR,Kim ME,et al.Morin attenuates tauhyperphosphorylation by inhibiting GSK3β.NeurobiolDis,2011,44(2):223-30
[9]Bretteville A,Marcouiller F,Julien C,et al.Hypothermia-induced hyperphosphorylation:a new model to study taukinase inhibitors.Sci Rep,2012,2:480
[10]Alonso AD,Di Clerico J,Li B,et al.Phosphorylation oftau at Thr212,Thr231,and Ser262 combined causesneurodegeneration.J Biol Chem,2010,285(40):30851-60
[11]Idan-Feldman A,Ostritsky R,Gozes I.Tau and caspase 3as targets for neuroprotection.Int J Alzheimers Dis,2012,2012:493670
[12]Jin M,Shepardson N,Yang T,et al.Soluble amyloidβ-protein dimers isolated from Alzheimer cortex directlyinduce Tau hyperphosphorylation and neuritic degeneration.Proc Natl Acad Sci USA,2011,108(14):5819-24
[13]Whittington RA,Virag L,Marcouiller F,et al.Propofoldirectly increases tau phosphorylation.PLoS One,2011,6(1):e16648
[14]Stein JL,Medland SE,Vasquez AA,et al.Identification ofcommon variants associated with human hippocampal andintracranial volumes.Nat Genet,2012,44(5):552-61
[15]Ikram MA,Fornage M,Smith AV,et al.Common variantsat 6q22 and 17q21 are associated with intracranial volume.Nat Genet,2012,44(5):539-44
[16]Metcalfe MJ,Huang Q,Figueiredo-Pereira ME.Coordination between proteasome impairment and caspaseactivation leading to TAU pathology:neuroprotection bycAMP.Cell Death Dis,2012,3:e326
[17]Yuzwa SA,Shan X,Macauley MS,et al.IncreasingO-GlcNAc slows neurodegeneration and stabilizes tauagainst aggregation.Nat Chem Biol,2012,8(4):393-9
[18]Nunes MA,Viel TA,Buck HS.Microdose lithiumtreatment stabilized cognitive impairment in patients withAlzheimer's disease.Curr Alzheimer Res,2013,10(1):104-7
[19]Zhou XW,Gustafsson JA,Tanila H,et al.Tau hyperphos-phorylation correlates with reduced methylation of proteinphosphatase 2A.Neurobiol Dis,2008,31(3):386-94
[20]Dai M,Zhang C,Kania U,et al.A PP6-type phosphataseholoenzyme directly regulates PIN phosphorylation andauxin efflux in Arabidopsis.Plant Cell,2012,24(6):2497-514
[21]Sun XY,Wei YP,Xiong Y,et al.Synaptic released zincpromotes tau hyperphosphorylation by inhibition ofprotein phosphatase 2A(PP2A).J Biol Chem,2012,287(14):11174-82
[22]Plouffe V,Mohamed NV,Rivest-McGraw J,et al.Hyperphosphorylation and cleavage at D421 enhance tausecretion.PLoS One,2012,7(5):e36873
[23]Sohrabi HR,Bates KA,Weinborn MG,et al.Olfactorydiscrimination predicts cognitive decline among community-dwelling older adults.Transl Psychiatry,2012,2:e118
[24]Carroll JC,Iba M,Bangasser DA,et al.Chronic stressexacerbates tau pathology,neurodegeneration,andcognitive performance through a corticotropin-releasingfactor receptor-dependent mechanism in a transgenicmouse model of tauopathy.J Neurosci,2011,31(40):14436-49
[25]LaPointe NE,Morfini G,Pigino G,et al.The aminoterminus of tau inhibits kinesin-dependent axonaltransport:implications for filament toxicity.J NeurosciRes,2009,87(2):440-51
[26]Medina DX,Caccamo A,Oddo S.Methylene blue reducesAβlevels and rescues early cognitive deficit by increasingproteasome activity.Brain Pathol,2011,21(2):140-9
[27]Wang Y,Martinez-Vicente M,Kruger U,et al.Taufragmentation,aggregation and clearance:the dual role oflysosomal processing.Hum Mol Genet,2009,18(21):4153-70
[28]Luo W,Dou F,Rodina A,et al.Roles of heat-shockprotein 90 in maintaining and facilitating the neurode-generative phenotype in tauopathies.Proc Natl Acad SciUSA,2007,104(22):9511-6
[29]Funderburk SF,Marcellino BK,Yue Z.Cell"self-eating"(autophagy)mechanism in Alzheimer's disease.Mt Sinai JMed,2010,77(1):59-68
[30]Hung SY,Huang WP,Liou HC,et al.Autophagy protectsneuron from Aβ-induced cytotoxicity.Autophagy,2009,5(4):502-10
[31]Ling D,Song HJ,Garza D,et al.Aβ42-induced neurode-generation via an age-dependent autophagic-lysosomalinjury in Drosophila.PLoS One,2009,4(1):e4201