The NRF2 activator RTA-408 ameliorates chronic alcohol exposure-induced cognitive impairment and NLRP3 inflammasome activation by modulating impaired mitophagy initiation.

Background: Chronic alcohol exposure induces cognitive impairment and NLRP3 inflammasome activation in the mPFC (medial prefrontal cortex). Mitophagy plays a crucial role in neuroinflammation, and dysregulated mitophagy is associated with behavioral deficits. However, the potential relationships among mitophagy, inflammation, and cognitive impairment in the context of alcohol exposure have not yet been studied.

Activation of STING signaling aggravates chronic alcohol exposure-induced cognitive impairment by increasing neuroinflammation and mitochondrial apoptosis.

Aims: Chronic alcohol exposure leads to persistent neurological disorders, which are mainly attributed to neuroinflammation and apoptosis. Stimulator of IFN genes (STING) is essential in the cytosolic DNA sensing pathway and is involved in inflammation and cellular death processes. This study was to examine the expression pattern and biological functions of STING signaling in alcohol use disorder (AUD).