The Roles Of Protein Phosphatase 2A In Tau Phosphorylation And Neuronal Survial

Hyper-phosphorylated tau is the major component of inclusions seen in Alzheimer's disease(AD)and other related neurodegenerative tauopathies.Under normal conditions,tau is a highly soluble protein.However,it undergoes several post-translational modifications resulting in fibrillization into straight-and paired-helical filaments(NFTs).Paired-helical filaments coalesce to form neurofibrillary tangles,the hallmark lesions in Alzheimer's disease.Significantly,the burden of tau pathology correlates well with clinical symptoms of dementia in AD.Protein phosphatase 2A(PP2A)is the predominant serine/threonine phosphatase in eukaryotic cells.It plays important roles in the network of cellular signal pathways.PP2A is the key tau phosphatase accounting for 71%of total tau dephosphorylation.In AD,PP2A activity is decreased.Reduced phosphatase activities have been observed in postmortem brains from AD patients.There have also been reports of inhibitors of PP2A that result in cardinal features of AD.All those suggest that decreased PP2A activity is required in NFT formation.This article mainly discusses on how the loss of PP2A function by conditional gene knock-out contributes to the progress of AD,and cast light on the pharmacology development against AD.