Shedding new light on methylmercury-induced neurotoxicity through the crosstalk between autophagy and apoptosis.

[Display omitted] • Summarizes the molecular mechanisms of autophagy and apoptosis in MeHg neurotoxicity. • Analyzes the relationship between autophagy and apoptosis in MeHg neurotoxicity. • Autophagic pathway may mitigate MeHg neurotoxicity through modulation of apoptosis. Methylmercury (MeHg) is a bio-accumulative global environmental contaminant present in fish and seafood. MeHg accumulates in the aquatic environment and eventually reaches the human system via the food chain by bio-magnification. The central nervous system is the primary target of toxicity and is particularly vulnerable during development. It is well documented that developmental MeHg exposure can lead to neurological alterations, including cognitive and motor dysfunction. Apoptosis is a primary characteristic of MeHg-induced neurotoxicity, and may be regulated by autophagic activity. However, mechanisms mediating the interaction between apoptosis and autophagy remains to be explored. Autophagy is an adaptive response under stressful conditions, and the basal level of autophagy ensures the physiological turnover of old and damaged organelles. Autophagy can regulate cell fate through different crosstalk signaling pathways. A complex interplay between autophagy and apoptosis determines the degree of apoptosis and the progression of MeHg-induced neurotoxicity as demonstrated by pre-clinical models and clinical trials. This review summarizes recent advances in the roles of autophagy and apoptosis in MeHg neurotoxicity and thoroughly explores the relationship between them. The autophagic pathway may be a potential therapeutic target in MeHg neurotoxicity through modulation of apoptosis. [ABSTRACT FROM AUTHOR]