Abolishing Tau cleavage by caspases at Aspartate⁴²¹ causes memory/synaptic plasticity deficits and pre-pathological Tau alterations.

ABSTRACT: TAU mutations are genetically linked to fronto-temporal dementia (FTD) and hyper-phosphorylated aggregates of Tau form neurofibrillary tangles (NFTs) that constitute a pathological hallmark of Alzheimer disease (AD) and FTD. These observations indicate that Tau has a pivotal role in the pathogenesis of neurodegenerative disorders. Tau is cleaved by caspases at Aspartate⁴²¹, to form a Tau metabolite known as δTau; δTau is increased in AD, due to the hyper-activation of caspases in AD brains. δTau is considered a critical toxic moiety underlying neurodegeneration, which initiates and facilitates NFT formation. As Tau is a therapeutic target in neurodegeneration, it is important to rigorously determine whether δTau is a toxic Tau species that should be pharmacologically attacked. T

SUBMITTER: Biundo F 

PROVIDER: S-EPMC5611732 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature