Protein phosphatase 2A, a key player in Alzheimer’s disease

Abstract

Protein phosphatase 2A (PP2A) is the predominant serine/threonine phosphatase in eukaryotic cells. In the brains of patients with Alzheimer’s disease (AD), decreased PP2A activities were observed, which is suggested to be involved in neurofibrillary tangle (NFT) formation, disturbed amyloid precursor protein (APP) secretion and neurodegeneration in AD brain. Based on our research and other previous findings, decreased PP2Ac level, decreased PP2A holoenzyme composition, increased level of PP2A inhibitors, increased PP2Ac Leu309 demethylation and Tyr307 phosphorylation underlie PP2A inactivation in AD. β-amyloid (Aβ) over-production, estrogen deficiency and impaired homocysteine metabolism are the possible up-stream factors that inactivate PP2A in AD neurons. Further studies are required to disclose the role of PP2A in Alzheimer’s disease.

Key words： protein phosphatase 2A; Alzheimer’s disease; holoenzyme composition; protein phosphatase 2A inhibitors; Leu309 demethylation; Tyr307 phosphorylation

Acknowledgements

This work was supported partially by the National Natural Science Foundation of China (Grant Nos. 30500188, 30871035 and 30731160621).

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