PP2A and Alzheimer Disease

Author(s): L. Torrent, I. Ferrer.

Journal Name: Current Alzheimer Research

Volume 9 , Issue 2 , 2012

Become EABM
Become Reviewer

Abstract:

Phosphorylation and, therefore, binding capacity of microtubule-associated protein tau is regulated by specific kinases and phosphatases. Activation of tau kinases plays a crucial role in tau- hyper-phosphorylation in Alzheimer disease (AD) and related tauopathies. Among phosphatases, protein phosphatase 2A, PP2A, is a principal tau dephosphorylating enzyme in the brain. PP2A acts as trimer composed of a catalytic (PP2A C), a scaffolding (PP2A A) and a regulatory (PP2 AB; B55α) subunit. Several abnormalities of PP2A have been reported in AD, including decreased mRNA and protein levels of the PP2A C (not replicated by other studies); decreased protein levels of the PP2A A and B55α; reduced PP2A C methylation at Leu309 due to impaired function methyltransferase type IV; increased PP2A C phosphorylation at Tyr307; up-regulation of the PP2A inhibitors I1 and I2; and loss of enzymatic activity. These observations indicate that PP2A is a putative target of therapeutic intervention considering that enhancing PP2A activity would decrease tau hyper-phosphorylation in AD. In spite of these achievements further studies are needed to replicate the reported individual different alterations converging in PP2A in AD.

Keywords: Alzheimer disease, protein phosphatase 2 A, methylation, phosphorylation

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 9
ISSUE: 2
Year: 2012
Page: [248 - 256]
Pages: 9
DOI: 10.2174/156720512799361682
Price: $58

Article Metrics

PDF: 18