Yang Xinyan, Chen Yinyu, Zheng Gaolin, Nie Qianyun, Zhang Peng
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Forensic Medicine, Hainan Provincial Tropical Forensic Engineering Research Center, Hainan Medical University, Haikou 571199, China.
Department of Pathology, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou 571199, China.
Int J Mol Sci. 2025 May 15;26(10):4732. doi: 10.3390/ijms26104732.
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 Ca uptake, MCU dysfunction can lead to Ca 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 Ca accumulation and mitochondrial dysfunction, ultimately leading to neuronal injury. Although MCU inhibitors have demonstrated potential in alleviating Ca 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.
随着社会的快速变化和压力水平的不断增加，精神活性物质的滥用已成为一场全球健康危机。研究表明，线粒体钙单向转运体（MCU）在精神活性物质诱导的神经毒性损伤中起关键作用。作为线粒体摄取钙的主要通道，MCU功能障碍可导致钙超载、氧化应激和细胞凋亡，这是神经毒性损伤的关键机制。3,4-亚甲基二氧甲基苯丙胺（摇头丸）、可卡因和吗啡等精神活性物质通过多种途径影响MCU功能，导致钙过度积累和线粒体功能障碍，最终导致神经元损伤。尽管MCU抑制剂在初步研究中已显示出减轻钙超载和改善神经功能的潜力，但其选择性和长期安全性仍需进一步评估。未来的研究应探索MCU在精神活性物质诱导的神经毒性损伤中的精确调控机制，并制定更有效的靶向治疗策略。
