Inhibition of death-associated protein kinase 1 attenuates cis P-tau and neurodegeneration in traumatic brain injury.

ABSTRACT: Traumatic brain injury (TBI) is the leading cause of mortality and disability in young people and may lead to the development of progressive neurodegeneration, such as that observed in chronic traumatic encephalopathy. We have recently found that the conformation-specific cis phosphorylated form of tau (cis P-tau) is a major early driver of neurodegeneration after TBI. However, not much is known about how cis P-tau is regulated in TBI. In this study, we demonstrated a novel critical role of death-associated protein kinase 1 (DAPK1) in regulating cis P-tau induction after TBI. We found that DAPK1 is significantly upregulated in mouse brains after TBI and subsequently promotes cis P-tau induction. Genetic deletion of DAPK1 in mice not only significantly decreases cis P-tau expression, but al

SUBMITTER: Kim N 

PROVIDER: S-EPMC8217320 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature