PP2A and Alzheimer Disease

Title: PP2A and Alzheimer Disease

Volume: 9 Issue: 2

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

Affiliation:

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

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.

Cite this article as:

Torrent L. and Ferrer I., PP2A and Alzheimer Disease, Current Alzheimer Research 2012; 9 (2) . https://dx.doi.org/10.2174/156720512799361682