Journal
CURRENT ALZHEIMER RESEARCH
Volume 9, Issue 2, Pages 248-256Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156720512799361682
Keywords
Alzheimer disease; protein phosphatase 2 A; methylation; phosphorylation
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Funding
- [PI080582]
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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; B55 alpha) 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 B55 alpha; 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 I-1 and I-2; 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.
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