Role of Protein Phosphatase 2A in Alzheimer's Disease

被引：35

作者：

Rudrabhatla, P. ^{[1
]}

Pant, H. C. ^{[1
]}

机构：

[1] NINDS, Cytoskeletal Regulatory Prot Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA

来源：

CURRENT ALZHEIMER RESEARCH | 2011年 / 8卷 / 06期

关键词：

Alzheimer's disease; tau; Neurofilaments; protein dephosphorylation; protein kinases and phosphatases; protein phosphatase 2A; Pin1; MICROTUBULE-ASSOCIATED PROTEINS; SERINE THREONINE PHOSPHATASES; XENOPUS-LAEVIS OOCYTES; RABBIT SKELETAL-MUSCLE; TAU-PROTEIN; NEUROFILAMENT PHOSPHORYLATION; CATALYTIC SUBUNIT; TRANSGENIC MICE; NEUROFIBRILLARY DEGENERATION; PHOSPHOTYROSYL PHOSPHATASE;

D O I：

10.2174/156720511796717168

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Alzheimer disease (AD) is the most common cause of dementia in adults. Aberrant hyperphosphorylation of microtubule associated protein Tau and neurofilament-M/H is one of the pathological hallmarks of AD. Most of the therapeutic strategies for treating AD are based on the inhibition of protein kinases such as glycogen synthase kinase-3 beta, cyclin-dependent kinase 5, and other Tau kinases. Here, we focus on protein phosphatase 2A (PP2A) as a key player in AD. PP2A expression and activity are downregulated in AD brain, contributing to the aberrant phosphorylation of Tau and NF proteins in AD. Recent data published from our lab as well as others on PP2A deregulation in AD is reviewed. The role of peptidyl prolyl isomerase Pin1 in regulation of PP2A mediated neurodegeneration is further analyzed. Development of drugs for AD could be based on restoration of PP2A activity or targeting Pin1.

引用

页码：623 / 632

页数：10

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