centrosome α β 3 25nm 2-1 minus end α plus end β 肌球蛋白 tracts motor proteins cargoes Va 动力蛋白 fast and slow axonal transport 1 3

Size: px

Start display at page:

Download "centrosome α β 3 25nm 2-1 minus end α plus end β 肌球蛋白 tracts motor proteins cargoes Va 动力蛋白 fast and slow axonal transport 1 3"

屯蔚
7 years ago
Views:

1 33 2 Vol 33 No Journal of South-Central University for NationalitiesNat Sci Edition Jun R741 02Q2 A Axonal Transport and Alzheimer's Disease Dai Jiapei 12 Wang Yanzi 12 1 Wuhan Institute for Neuroscience and NeuroengineeringSouth-Central University for NationalitiesWuhan College of Life SciencesSouth-Central University for NationalitiesWuhan China Abstract A neuron has the unique branch structure that can connect with other neurons to build up the functional neural circuits to ensure the neural signal transmission and the other neural functions Axonal transport is very important to maintain the structure and function of a neuron Previous researches have demonstrated that the coordination and integration of microtubulesmolecular motors and other associated factors provided the important molecular bases for axonal transport A large number of studies have suggested that axonal transport deficits are related to the cause and development of Alzheimer's disease This paper briefly reviewed the current research progress in this area and explained the relationship between axonal transport deficits and Alzheimer's disease Keywords Alzheimer's diseaseaxonal transport deficitsaxonal leakagemolecular motor axons dendrites AD axonal transport NFT SPs axonal transport deficits or impaired axonal transportad jdai@ mail scuec edu cn XJS9001 CJS13001

2 centrosome α β 3 25nm 2-1 minus end α plus end β 肌球蛋白 tracts motor proteins cargoes Va 动力蛋白 fast and slow axonal transport 1 3 microtubule-associated proteinmap molecular motors ATP MAP2 MAP1 Tau 4 Tau MAP2 Tau MAP2 AD anterograde direction Tau 蛋白 Tau autophagosomes 1 Tau Tau MAP2 MAP2 kinesin dynein myosin Tg2576 Aβ42 MAP2 MAP 驱动蛋白 AD E4 ApoE4 ApoE4 2-1cytoplasm dynein 1 Va

3 38 33 MG-115 Tau 12 Tau APP PS1 Aβ AD 6 β β-secretase BACE APP Aβ Aβ Tau Tau AD Tau 13 APP Aβ Tau 4 Tau 14 Tau axonal dilations AD PP1 GSK3β KLCs axonopathy AD AD AD Tau AD AD SPs NFTs 8 AD Tau glucocorticoid resistance Goldstein PS1 Tau AD Tau 蛋白与轴突转运障碍 Tau AD AD APP Tau Tau TG-swAPPprp -1kinesin-1 KLC1wt /KLC1wt 9 15 Tau swelling of axon and varicosity Tau Tau AD Tau Aβ Tau Tau 16 Tau AD AD AD AD APP 与轴突转运障碍 APP 1 PS1β 1 AD BACE1 KLCs

4 2 39 nerve growth factorngf streptozotocinstz APP swapp 3 ~ 4 I 2 dendropathy 25 internalization AD dyingback pattern endosome 17 Aβ AD 26 α- Aβ MEC-17 Aβ NMDA GSK3β 27 A- AMP NMDA 18 APP Aβ42 brainderived neurotrophic factorbdnf -2 BDNF 19 AD 20 APP Tau 轴突漏与轴突转运障碍 AD AD axonal leakagead SPs NFTs AD AD AD 其他 AD 相关因素与轴突转运障碍 1Maday SWallace K EHolzbaur E L Autophagosomes AD initiate distally and mature during transport toward the cell soma in primary neurons J Cell Biol Wistar / Hirokawa NNiwa STanaka Y Molecular motors in 30min / neurons transport mechanisms and roles in brain 6h 4 Dupuis L Cytoplasmic dynein in neurode- Pharmacol Ther Dong X P Dysfunction of microtubule-associated proteins of MAP2 /tau family J Prion traumatic brain injurytbi AD 3Eschbach J AD generation J 23 SD 4Zhang J 3h 24h functiondevelopment and disease J Neuron2010 APP 24 5Takahashi R H Capetillo-Zarate E Lin M T et al Accu-

5 40 33 mulation of intreneuronal β-amyloid 42 peptides is associated with early changes in microtubule-associated protein 2 in neuritis and synapses J PLoS One e Agholme L Nath S Domert J et al Proteasome inhibition induces stress kinase dependent transport deficits- Implications for Alzheimer ' s disease J Mol Cell Neurosci Buggia-Prévot V Fernandez C G Udayar V et al A function for EHD family proteins in unidirectional retrograde dendritic transport of BACE1 and Alzheimer's disease Aβ production J Cell Rep Dai JBuijs R MKamphorst Wet al Impaired axonal transport of cortical neurons in Alzheimer' s disease is associated with neuropathological changes J Brain Res / Stokin G BLillo CFalzone T Let al Axonopathy and transport deficits early in the pathogenesis of Alzheimer' s disease J Science Minoshima S Cross D In vivo imaging of axonal transport using MRIaging and Alzheimer' s disease J Eur J Nucl Med Mol Imaging200835Sup 1 S89-S92 11 Adalbert RNogradi ABabetto Eet al Severely dystrophic axons at amyloid plaques remain continuous and connected to viable cell bodies J Brain Pt Zhao X LWang W ATan J Xet al Expression of beta-amyloid induced agedependent presynaptic and axonal changes in Drosophila J Neurosci McVicker D PChrin L RBerger C L The nucleotidebinding state of microtubules modulates kinesin processivity and the ability of Tau to inhibit kinesinmediated transport J Biol Chem Morfini GPigino GMizuno Net al Tau binding to microtubules does not directly affect microtubule-based vesicle motility J Neurosci Res Yuan AKumar APeterhoff Cet al Axonal transport rates in vivo are unaffected by tau deletion or overexpression in mice J Neurosci Cowan C MMudher A Are tau aggregates toxic or protective in tauopathies J Front Neurol Salehi ADelcroix J DBelichenko P Vet al Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration J Neuron Decker HLo K YUnger S Met al Amyloid-β peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3β in primary cultured hippocampus neurons J Neurosci Poon W WBlurton-Jones MTu C Het al β- Amyloid impairs axonal BDNF retrograde trafficking J Neurobiol Aging Reddy P HTripathi RTriung Q et al Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer' s diseaseimplications to mitochondria-targeted antioxidant therapeutics J Biochim Biophys Acta Xiao A W He J Wang Q et al The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer' s disease J Neurosci Bull Krstic D Knuesel I Deciphering the mechanism underlying late-onset Alzheimer' s disease J Nat Rev Neurol Namjoshi D RMartin GDonkin Jet al The liver X receptor agonist GW3965 improves recovery from mild repetitive traumatic brain injury in mice partly through apolipoprotein E J PLoS One Li SSun YShan Det al Temporal profiles of axonal injury following impact acceleration traumatic brain injury in rats--a comparative study with diffusion tensor imaging and morphological analysis J Int J Legal Med Zhou YLuo YDai J Axonal and dendritic changes are associated with diabetic encephalopathy in ratsan important risk factor for Alzheimer' s disease J J Alzheimer's Dis Kanaan N MPigino G FBrady S Tet al Axonal degeneration in Alzheimer' s diseasewhen signaling abnormalities meet the axonal transport system J Exp Neurol Neumann BHilliard M A Loss of MEC-17 leads to microtubule instability and axonal degeneration J Cell rep

淺談保健食材與阿茲海默氏症之預防食營系詹吟菁特聘教授由於醫療的進步及人民生活品質的改善, 平均壽命得以延長, 罹患退化性疾病的人口也隨之增多而退化性疾病的患

淺談保健食材與阿茲海默氏症之預防食營系詹吟菁特聘教授由於醫療的進步及人民生活品質的改善, 平均壽命得以延長, 罹患退化性疾病的人口也隨之增多而退化性疾病的患各位親愛的系友們, 大家好! 在邁入 2016 年之初, 再次感謝前輩師長及系友們 40 年來在協助母系發展方面所付出之心血及系友們不斷的鼓勵與支持母系在全體師生共同努力經營之下, 始終穩定的成長且屢獲佳績首先恭賀 104 學年度獲