Tau in Alzheimer's Disease: Mechanisms and Therapeutic Strategies

被引：252

作者：

Gao, Yu ^{[1
]}

Tan, Lin ^{[1
,2
]}

Yu, Jin-Tai ^{[1
]}

Tan, Lan ^{[1
]}

机构：

[1] Qingdao Univ, Qingdao Municipal Hosp, Sch Med, Dept Neurol, Qingdao, Peoples R China

[2] Ocean Univ China, Coll Med & Pharmaceut, Qingdao, Peoples R China

来源：

CURRENT ALZHEIMER RESEARCH | 2018年 / 15卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Tau; aggregation; phosphorylation; NFTs; Alzheimer's disease; therapy; AGGREGATION INHIBITOR THERAPY; DIET-INDUCED OBESITY; PATHOLOGICAL TAU; MOUSE MODEL; PHOSPHORYLATED TAU; AMYLOID-BETA; IN-VITRO; A-BETA; PROMOTES NEURODEGENERATION; CEREBROSPINAL-FLUID;

D O I：

10.2174/1567205014666170417111859

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: Alzheimer's disease (AD), the most important progressive neurodegenerative disorder, is characterized by cognitive and behavioral disabilities. Nowadays, tau, as a microtubule-associated protein and a principle neuropathological hallmark of AD, provides us a neoteric perspective to explore further aetiopathogenesis and therapeutic strategy. The hyperphosphorylation and abnormal aggregation of tau, combined with its decreased clearance, form neurofibrillary tangles (NFTs) and exert neurotoxicity in AD. Methods: Recent investigations aim to prevent the deposition of NFT and accelerate the clearance of NFT. Intriguingly, immunization strategies targeting tau effectively ameliorates the tau-associated pathology in AD. In addition, modified therapies targeting tau should be regarded as a potential way to treat AD. These progresses open new avenues for AD. Conclusion: Here, we review the recent literature of potential mechanisms of the tau in AD and discuss the modified therapeutic strategies for AD.

引用

页码：283 / 300

页数：18

共 183 条

[41] Alternative polyadenylation and miR-34 family members regulate tau expression [J].

Dickson, John R. ;

Kruse, Carla ;

Montagna, Daniel R. ;

Finsen, Bente ;

Wolfe, Michael S. .

JOURNAL OF NEUROCHEMISTRY, 2013, 127 (06) :739-749

[42] A Caspase Cleaved Form of Tau Is Preferentially Degraded through the Autophagy Pathway [J].

Dolan, Philip J. ;

Johnson, Gail V. W. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (29) :21978-21987

[43] Inhibitory Act of Selenoprotein P on Cu+/Cu2+-Induced Tau Aggregation and Neurotoxicity [J].

Du, Xiubo ;

Zheng, Youbiao ;

Wang, Zhi ;

Chen, Yijing ;

Zhou, Rui ;

Song, Guoli ;

Ni, Jiazuan ;

Liu, Qiong .

INORGANIC CHEMISTRY, 2014, 53 (20) :11221-11230

[44] March separate, strike together - Role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer's disease [J].

Eckert, Anne ;

Nisbet, Rebecca ;

Grimm, Amandine ;

Goetz, Juergen .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2014, 1842 (08) :1258-1266

[45] Association of APOE with tau-tangle pathology with and without β-amyloid [J].

Farfel, Jose M. ;

Yu, Lei ;

De Jager, Philip L. ;

Schneider, Julie A. ;

Bennett, David A. .

NEUROBIOLOGY OF AGING, 2016, 37 :19-25

[46] Tau Binds ATP and Induces Its Aggregation [J].

Farid, Mina ;

Corbo, Christopher P. ;

Alonso, Alejandra Del C. .

MICROSCOPY RESEARCH AND TECHNIQUE, 2014, 77 (02) :133-137

[47] Cellular factors modulating the mechanism of tau protein aggregation [J].

Fontaine, Sarah N. ;

Sabbagh, Jonathan J. ;

Baker, Jeremy ;

Martinez-Licha, Carlos R. ;

Darling, April ;

Dickey, Chad A. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2015, 72 (10) :1863-1879

[48] Peripheral hyperinsulinemia promotes tau phosphorylation in vivo [J].

Freude, S ;

Plum, L ;

Schnitker, J ;

Leeser, U ;

Udelhoven, M ;

Krone, W ;

Bruning, JC ;

Schubert, M .

DIABETES, 2005, 54 (12) :3343-3348

[49] Connecting the dots between tau dysfunction and neurodegeneration [J].

Frost, Bess ;

Goetz, Juergen ;

Feany, Mel B. .

TRENDS IN CELL BIOLOGY, 2015, 25 (01) :46-53

[50] Tau promotes neurodegeneration through global chromatin relaxation [J].

Frost, Bess ;

Hemberg, Martin ;

Lewis, Jada ;

Feany, Mel B. .

NATURE NEUROSCIENCE, 2014, 17 (03) :357-U48

← 1 2 3 4 5 6 7 8 9 10 →