Protein Phosphatases and Alzheimer's Disease

被引：84

作者：

Braithwaite, Steven P. ^{[1
]}

Stock, Jeffry B. ^{[2
]}

Lombroso, Paul J. ^{[3
]}

Nairn, Angus C. ^{[4
]}

机构：

[1] Signum Biosci, Monmouth Jct, NJ USA

[2] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA

[3] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA

[4] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA

来源：

PROTEIN PHOSPHORYLATION IN HEALTH AND DISEASE | 2012年 / 106卷

关键词：

AMYLOID PRECURSOR PROTEIN; LONG-TERM POTENTIATION; UBIQUITIN-PROTEASOME SYSTEM; DEPENDENT AXONAL-TRANSPORT; NMDA RECEPTOR TRAFFICKING; TYROSINE-PHOSPHATASE; A-BETA; CATALYTIC SUBUNIT; AMPA RECEPTOR; SERINE/THREONINE PHOSPHATASES;

D O I：

10.1016/B978-0-12-396456-4.00012-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alzheimer's Disease (AD) is characterized by progressive loss of cognitive function, linked to marked neuronal loss. Pathological hallmarks of the disease are the accumulation of the amyloid-beta (A beta) peptide in the form of amyloid plaques and the intracellular formation of neurofibrillary tangles (NFTs). Accumulating evidence supports a key role for protein phosphorylation in both the normal and pathological actions of A beta as well as the formation of NFTs. NFTs contain hyperphosphorylated forms of the microtubule-binding protein tau, and phosphorylation of tau by several different kinases leads to its aggregation. The protein kinases involved in the generation and/or actions of tau or A beta are viable drug targets to prevent or alleviate AD pathology. However, it has also been recognized that the protein phosphatases that reverse the actions of these protein kinases are equally important. Here, we review recent advances in our understanding of serine/threonine and tyrosine protein phosphatases in the pathology of AD.

引用

页码：343 / 379

页数：37

共 250 条

[1] Proteolysis of calcineurin is increased in human hippocampus during mild cognitive impairment and is stimulated by oligomeric Abeta in primary cell culture [J].