Abstract
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-3β, 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.
Keywords: Alzheimer's disease, tau, Neurofilaments, protein dephosphorylation, protein kinases, phosphatases, protein phosphatase 2A, Pin1, NFT, progressive dementia, hyperphosphorylation, Tau mutation, cerebral infusion, FTDP17
Current Alzheimer Research
Title: Role of Protein Phosphatase 2A in Alzheimers Disease
Volume: 8 Issue: 6
Author(s): P. Rudrabhatla and H. C. Pant
Affiliation:
Keywords: Alzheimer's disease, tau, Neurofilaments, protein dephosphorylation, protein kinases, phosphatases, protein phosphatase 2A, Pin1, NFT, progressive dementia, hyperphosphorylation, Tau mutation, cerebral infusion, FTDP17
Abstract: 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-3β, 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.
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Cite this article as:
Rudrabhatla P. and C. Pant H., Role of Protein Phosphatase 2A in Alzheimers Disease, Current Alzheimer Research 2011; 8 (6) . https://dx.doi.org/10.2174/156720511796717168
DOI https://dx.doi.org/10.2174/156720511796717168 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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