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

[31] A role for FKBP52 in Tau protein function [J].

Chambraud, Beatrice ;

Sardin, Elodie ;

Giustiniani, Julien ;

Dounane, Omar ;

Schumacher, Michael ;

Goedert, Michel ;

Baulieu, Etienne-Emile .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (06) :2658-2663

[32] The acetylation of tau inhibits its function and promotes pathological tau aggregation [J].

Cohen, Todd J. ;

Guo, Jing L. ;

Hurtado, David E. ;

Kwong, Linda K. ;

Mills, Ian P. ;

Trojanowski, John Q. ;

Lee, Virginia M. Y. .

NATURE COMMUNICATIONS, 2011, 2

[33] Cdk5 deregulation in the pathogenesis of Alzheimer's disease [J].

Cruz, JC ;

Tsai, LH .

TRENDS IN MOLECULAR MEDICINE, 2004, 10 (09) :452-458

[34] Tau Passive Immunotherapy in Mutant P301L Mice: Antibody Affinity versus Specificity [J].

d'Abramo, Cristina ;

Acker, Christopher M. ;

Jimenez, Heidy T. ;

Davies, Peter .

PLOS ONE, 2013, 8 (04)

[35]

Dalla C, 2011, CURR TOP BEHAV NEURO, V8, P97, DOI 10.1007/7854_2010_94

[36] Imaging biomarkers in tauopathies [J].

Dani, Melanie ;

Edison, Paul ;

Brooks, David J. .

PARKINSONISM & RELATED DISORDERS, 2016, 22 :S26-S28

[37]

Dawson HN, 2001, J CELL SCI, V114, P1179

[38] The Role of Tau Oligomers in the Onset of Alzheimer's Disease Neuropathology [J].

del Carmen Cardenas-Aguayo, Maria ;

Gomez-Virgilio, Laura ;

DeRosa, Steven ;

Antonio Meraz-Rios, Marco .

ACS CHEMICAL NEUROSCIENCE, 2014, 5 (12) :1178-1191

[39] Amyloid-β-Associated Clinical Decline Occurs Only in the Presence of Elevated P-tau [J].

Desikan, Rahul S. ;

McEvoy, Linda K. ;

Thompson, Wesley K. ;

Holland, Dominic ;

Brewer, James B. ;

Aisen, Paul S. ;

Sperling, Reisa A. ;

Dale, Anders M. .

ARCHIVES OF NEUROLOGY, 2012, 69 (06) :709-713

[40] Deletion of the ubiquitin ligase CHIP leads to the accumulation, but not the aggregation, of both endogenous phospho- and caspase-3-cleaved tau species [J].

Dickey, Chad A. ;

Yue, Mei ;

Lin, Wen-Lang ;

Dickson, Dennis W. ;

Dunmore, Judith H. ;

Lee, Wing C. ;

Zehr, Cynthia ;

West, Gemma ;

Cao, Songsong ;

Clark, Amber M. K. ;

Caldwell, Guy A. ;

Caldwell, Kim A. ;

Eckman, Christopher ;

Patterson, Cam ;

Hutton, Michael ;

Petrucelli, Leonard .

JOURNAL OF NEUROSCIENCE, 2006, 26 (26) :6985-6996

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