PP2A and Alzheimer disease.
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.
Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Hospitalet de LLobregat, Spain.
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D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000201:enzymology*; D005260:Female; D006801:Humans; D007206:Individuality; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D054648:Protein Phosphatase 2 / Q000378:metabolism*
D054648:Protein Phosphatase 2