Mitochondrial Calcium Uniporter (MCU)-Mediated Calcium Overload in Psychoactive Drug Neurotoxicity: From Pathogenesis to Therapeutic Targets.

The mitochondrial calcium uniporter (MCU) is a key channel for calcium uptake into mitochondria, and its dysfunction contributes to neurotoxic damage from psychoactive substances like MDMA, cocaine, and morphine. MCU dysfunction causes calcium overload, oxidative stress, and apoptosis, leading to neuronal injury. While MCU inhibitors show promise in reducing calcium overload and improving neural function, their selectivity and long-term safety need further study. Future research should focus on the precise regulatory mechanisms of MCU in drug-induced neurotoxicity and the development of targeted therapies.

Study at a glance

Abstract

With rapid societal changes and increasing stress levels, the abuse of psychoactive substances has emerged as a global health crisis. Studies indicate that the mitochondrial calcium uniporter (MCU) plays a pivotal role in neurotoxic damage induced by psychoactive substances. As the primary channel for mitochondrial Ca2+ uptake, MCU dysfunction can lead to Ca2+ overload, oxidative stress, and apoptosis, representing a crucial mechanism underlying neurotoxic damage. Psychoactive substances such as 3,4-Methylenedioxymethamphetamine (MDMA), cocaine, and morphine influence MCU function through multiple pathways, resulting in excessive Ca2+ accumulation and mitochondrial dysfunction, ultimately leading to neuronal injury. Although MCU inhibitors have demonstrated potential in alleviating Ca2+ overload and improving neural function in preliminary studies, their selectivity and long-term safety require further evaluation. Future research should explore the precise regulatory mechanisms of MCU in neurotoxic damage induced by psychoactive substances and develop more effective targeted therapeutic strategies.