SENP6-Mediated deSUMOylation of Nrf2 Exacerbates Neuronal Oxidative Stress Following Cerebral Ischemia and Reperfusion Injury.

ABSTRACT: Oxidative stress is believed to play critical pathophysiological roles in ischemic brain injury, and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is recognized as the most crucial endogenous antioxidant stress damage route. Some research have demonstrated that Nrf2 play critical roles in oxidative stress after ischemic stroke, but the underlying mechanism are not fully elucidated. This study reveals that Nrf2 is modified by SUMOylation and identifies Sentrin/SUMO-specific protease 6 (SENP6) as a negative regulator of Nrf2 SUMOylation. Notably, SENP6 binds to and mediates the deSUMOylation of Nrf2, which in turn inhibits antioxidant response by enhancing ubiquitination-dependent degradation of Nrf2, thereby reducing its transcriptional activity, inducing oxidativ

SUBMITTER: Xia Q 

PROVIDER: S-EPMC11831438 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature