Blocking ERK-DAPK1 Axis Attenuates Glutamate Excitotoxicity in Epilepsy.

ABSTRACT: Glutamate excitotoxicity induces neuronal cell death during epileptic seizures. Death-associated protein kinase 1 (DAPK1) expression is highly increased in the brains of epilepsy patients; however, the underlying mechanisms by which DAPK1 influences neuronal injury and its therapeutic effect on glutamate excitotoxicity have not been determined. We assessed multiple electroencephalograms and seizure grades and performed biochemical and cell death analyses with cellular and animal models. We applied small molecules and peptides and knocked out and mutated genes to evaluate the therapeutic efficacy of kainic acid (KA), an analog of glutamate-induced neuronal damage. KA administration increased DAPK1 activity by promoting its phosphorylation by activated extracellular signal-regulated kinase (

SUBMITTER: Gan CL 

PROVIDER: S-EPMC9223430 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature