Ethanol, neurosteroids and cellular stress responses: Impact on central nervous system toxicity, inflammation and autophagy

Abstract

Alcohol intake can impair brain function, in addition to other organs such as the liver and kidney. In the brain ethanol can be detrimental to memory formation, through inducing the integrated stress response/endoplasmic reticulum stress/unfolded protein response and the molecular mechanisms linking stress to other events such as NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammation and autophagy. This literature review aims to provide an overview of our current understanding of the molecular mechanisms involved in ethanol-induced damage with endoplasmic reticulum stress, integrated stress response, NLRP3 inflammation and autophagy, while discussing the impact of neurosteroids and oxysterols, including allopregnanolone, 25-hydroxycholesterol and 24S-hydroxycholesterol, on the central nervous system.

Keywords: 24S-Hydroxycholesterol; 25-Hydroxycholesterol; Acetaldehyde; Alcohol; Allopregnanolone; Apoptosis; Cell death; Cytokine; Fetal alcohol syndrome; Golgi apparatus; Hippocampus; Lipopolysaccharide; Liver X receptor; Long-term potentiation; Memory; Microglia; NLRP3; Neurotoxicity; Oxysterol; Quercetin; Reactive oxygen species; Salubrinal.