Acute inhibition of the CNS-specific kinase TTBK1 significantly lowers tau phosphorylation at several disease relevant sites.

ABSTRACT: Hyperphosphorylated tau protein is a pathological hallmark of numerous neurodegenerative diseases and the level of tau pathology is correlated with the degree of cognitive impairment. Tau hyper-phosphorylation is thought to be an early initiating event in the cascade leading to tau toxicity and neuronal death. Inhibition of tau phosphorylation therefore represents an attractive therapeutic strategy. However, the widespread expression of most kinases and promiscuity of their substrates, along with poor selectivity of most kinase inhibitors, have resulted in systemic toxicities that have limited the advancement of tau kinase inhibitors into the clinic. We therefore focused on the CNS-specific tau kinase, TTBK1, and investigated whether selective inhibition of this kinase could represent a vi

SUBMITTER: Dillon GM 

PROVIDER: S-EPMC7138307 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature