Peng Yichen, Zhou Li, Jin Yaju, Wu Danli, Chen Na, Zhang Chengcai, Liu Hongpeng, Li Chunlan, Ning Rong, Yang Xichen, Mao Qiuyue, Liu Jiaxin, Zhang Pengyue
Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Key Laboratory of Acupuncture and Massage for Treatment of Encephalopathy, College of Acupuncture, Tuina and Rehabilitation, Yunnan University of Chinese Medicine, Kunming, Yunnan Province, China.
School of Medicine, Kunming University of Science and Technology, Kunming, Yunnan Province, China.
Neural Regen Res. 2025 Dec 1;20(12):3349-3369. doi: 10.4103/NRR.NRR-D-24-00630. Epub 2024 Nov 13.
The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels. Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane, formed by various proteins and protein complexes. This microstructural domain mediates several specialized functions, including calcium (Ca 2+ ) signaling, autophagy, mitochondrial morphology, oxidative stress response, and apoptosis. Notably, the dysregulation of Ca 2+ signaling mediated by mitochondria-associated endoplasmic reticulum membranes is a critical factor in the pathogenesis of neurological diseases. Certain proteins or protein complexes within these membranes directly or indirectly regulate the distance between the endoplasmic reticulum and mitochondria, as well as the transduction of Ca 2+ signaling. Conversely, Ca 2+ signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membrane-associated functions. These functions can vary significantly across different neurological diseases-such as ischemic stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease-and their respective stages of progression. Targeted modulation of these disease-related pathways and functional proteins can enhance neurological function and promote the regeneration and repair of damaged neurons. Therefore, mitochondria-associated endoplasmic reticulum membranes-mediated Ca 2+ signaling plays a pivotal role in the pathological progression of neurological diseases and represents a significant potential therapeutic target. This review focuses on the effects of protein complexes in mitochondria-associated endoplasmic reticulum membranes and the distinct roles of mitochondria-associated endoplasmic reticulum membranes-mediated Ca 2+ signaling in neurological diseases, specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca 2+ overload or deficiency. This article provides a comprehensive analysis of the various mechanisms of Ca 2+ signaling mediated by mitochondria-associated endoplasmic reticulum membranes in neurological diseases, contributing to the exploration of potential therapeutic targets for promoting neuroprotection and nerve repair.
细胞器之间的信息和物质交换在调节细胞生理功能和代谢水平方面起着至关重要的作用。线粒体相关内质网膜作为内质网膜与线粒体外膜之间的物理接触通道，由各种蛋白质和蛋白质复合物形成。这个微结构域介导多种特殊功能，包括钙（Ca2+）信号传导、自噬、线粒体形态、氧化应激反应和细胞凋亡。值得注意的是，线粒体相关内质网膜介导的Ca2+信号失调是神经疾病发病机制中的一个关键因素。这些膜内的某些蛋白质或蛋白质复合物直接或间接调节内质网与线粒体之间的距离以及Ca2+信号的转导。相反，线粒体相关内质网膜介导的Ca2+信号会影响其他与线粒体相关内质网膜相关的功能。这些功能在不同的神经疾病（如缺血性中风、创伤性脑损伤、阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿舞蹈病）及其各自的进展阶段可能有显著差异。对这些疾病相关途径和功能蛋白的靶向调节可以增强神经功能并促进受损神经元的再生和修复。因此，线粒体相关内质网膜介导的Ca2+信号在神经疾病的病理进展中起关键作用，是一个重要的潜在治疗靶点。本综述重点关注线粒体相关内质网膜中蛋白质复合物的作用以及线粒体相关内质网膜介导的Ca2+信号在神经疾病中的不同作用，特别强调线粒体Ca2+长期过载或缺乏可能导致的早期保护作用及神经元损伤。本文全面分析了线粒体相关内质网膜在神经疾病中介导Ca2+信号的各种机制，有助于探索促进神经保护和神经修复的潜在治疗靶点。
