Tau Reduction Prevents Aβ-Induced Defects in Axonal Transport

被引：413

作者：

Vossel, Keith A. ^{[1
,2
]}

Zhang, Kai ^{[3
]}

Brodbeck, Jens ^{[1
]}

Daub, Aaron C. ^{[1
]}

Sharma, Punita ^{[1
]}

Finkbeiner, Steven ^{[1
,2
]}

Cui, Bianxiao ^{[3
]}

Mucke, Lennart ^{[1
,2
]}

机构：

[1] Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA

[3] Stanford Univ, Dept Chem, Stanford, CA 94305 USA

来源：

SCIENCE | 2010年 / 330卷 / 6001期

关键词：

ALZHEIMERS-DISEASE; AMYLOID-BETA; HIPPOCAMPAL-NEURONS; MOUSE MODEL; OVEREXPRESSION; TRAFFICKING; MECHANISM;

D O I：

10.1126/science.1194653

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Amyloid-beta (A beta) peptides, derived from the amyloid precursor protein, and the microtubule-associated protein tau are key pathogenic factors in Alzheimer's disease (AD). How exactly they impair cognitive functions is unknown. We assessed the effects of A beta and tau on axonal transport of mitochondria and the neurotrophin receptor TrkA, cargoes that are critical for neuronal function and survival and whose distributions are altered in AD. A beta oligomers rapidly inhibited axonal transport of these cargoes in wild-type neurons. Lowering tau levels prevented these defects without affecting baseline axonal transport. Thus, A beta requires tau to impair axonal transport, and tau reduction protects against A beta-induced axonal transport defects.

引用

页码：198 / U52

页数：2

共 12 条

[1] LOSS OF TAU ELICITS AXONAL DEGENERATION IN A MOUSE MODEL OF ALZHEIMER'S DISEASE [J].

Dawson, H. N. ;

Cantillana, V. ;

Jansen, M. ;

Wang, H. ;

Vitek, M. P. ;

Wilcock, D. M. ;

Lynch, J. R. ;

Laskowitz, D. T. .

NEUROSCIENCE, 2010, 169 (01) :516-531

[2] Amyloid-β Peptide Oligomers Disrupt Axonal Transport through an NMDA Receptor-Dependent Mechanism That Is Mediated by Glycogen Synthase Kinase 3β in Primary Cultured Hippocampal Neurons [J].

Decker, Helena ;

Lo, Karen Y. ;

Unger, Sandra M. ;

Ferreira, Sergio T. ;

Silverman, Michael A. .

JOURNAL OF NEUROSCIENCE, 2010, 30 (27) :9166-9171

[3] Differential regulation of dynein and kinesin motor proteins by tau [J].

Dixit, Ram ;

Ross, Jennifer L. ;

Goldman, Yale E. ;

Holzbaur, Erika L. F. .

SCIENCE, 2008, 319 (5866) :1086-1089

[4] Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: Implications for Alzheimer's disease [J].

Ebneth, A ;

Godemann, R ;

Stamer, K ;

Illenberger, S ;

Trinczek, B ;

Mandelkow, EM ;

Mandelkow, E .

JOURNAL OF CELL BIOLOGY, 1998, 143 (03) :777-794

[5] Mitochondrial abnormalities in Alzheimer's disease [J].

Hirai, K ;

Aliev, G ;

Nunomura, A ;

Fujioka, H ;

Russell, RL ;

Atwood, CS ;

Johnson, AB ;

Kress, Y ;

Vinters, HV ;

Tabaton, M ;

Shimohama, S ;

Cash, AD ;

Siedlak, SL ;

Harris, PLR ;

Jones, PK ;

Petersen, RB ;

Perry, G ;

Smith, MA .

JOURNAL OF NEUROSCIENCE, 2001, 21 (09) :3017-3023

[6]

Hiruma H, 2003, J NEUROSCI, V23, P8967

[7] Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer's Disease Mouse Models [J].

Ittner, Lars M. ;

Ke, Yazi D. ;

Delerue, Fabien ;

Bi, Mian ;

Gladbach, Amadeus ;

van Eersel, Janet ;

Woelfing, Heidrun ;

Chieng, Billy C. ;

Christie, MacDonald J. ;

Napier, Ian A. ;

Eckert, Anne ;

Staufenbiel, Matthias ;

Hardeman, Edna ;

Goetz, Juergen .

CELL, 2010, 142 (03) :387-397

[8] Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta [J].

Pigino, G. ;

Morfini, G. ;

Atagi, Y. ;

Deshpande, A. ;

Yu, C. ;

Jungbauer, L. ;

LaDu, M. ;

Busciglio, J. ;

Brady, S. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (14) :5907-5912

[9] Reducing endogenous tau ameliorates amyloid β-induced deficits in an Alzheimer's disease mouse model [J].

Roberson, Erik D. ;

Scearce-Levie, Kimberly ;

Palop, Jorge J. ;

Yan, Fengrong ;

Cheng, Irene H. ;

Wu, Tiffany ;

Gerstein, Hilary ;

Yu, Gui-Qiu ;

Mucke, Lennart .

SCIENCE, 2007, 316 (5825) :750-754

[10] Acute impairment of mitochondrial trafficking by β-amyloid peptides in hippocampal neurons [J].

Rui, Yanfang ;

Tiwari, Priyanka ;

Xie, Zuoping ;

Zheng, James Q. .

JOURNAL OF NEUROSCIENCE, 2006, 26 (41) :10480-10487

← 1 2 →