中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (12): 3349-3369.doi: NRR.NRR-D-24-00630

• 综述:退行性病与再生 •    下一篇

线粒体相关内质网膜构建钙桥：神经疾病修复的潜在靶点

  

  • 出版日期:2025-12-15 发布日期:2025-03-12

Calcium bridges built by mitochondria-associated endoplasmic reticulum membranes: potential targets for neural repair in neurological diseases

Yichen Peng1 , Li Zhou1 , Yaju Jin1 , Danli Wu1 , Na Chen1 , Chengcai Zhang1 , Hongpeng Liu1 , Chunlan Li1 , Rong Ning1 , Xichen Yang1 , Qiuyue Mao1 , Jiaxin Liu2, *, Pengyue Zhang1, *   

  1. 1 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;  2 School of Medicine, Kunming University of Science and Technology, Kunming, Yunnan Province, China
  • Online:2025-12-15 Published:2025-03-12
  • Contact: Pengyue Zhang, MD, zpy19802000@163.com; Jiaxin Liu, PhD, 20130141@kust.edu.cn.
  • Supported by:
    This work was supported by Yunnan Province Innovation Team of Prevention and Treatment for Brain Disease with Acupuncture and Tuina, No. 202405AS350007; Youth Top Talent Project of 10-thousand Talent Plan in Yunnan Province, No. YNWR-QNBJ-2018-345; the National Natural Science Foundation of China, No. 81960731; Joint Special Project of Traditional Chinese Medicine in Science and Technology Department of Yunnan Province, Nos. 2019FF002[-008], 202001AZ070001-002 and 202001AZ070001-030; Yunnan Province University Innovation Team Projects No. 2019YGC04; and Yunnan Province Project Education Fund, Nos. 2024Y406, 2024Y414 (all to PZ).

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摘要：

细胞器之间的信息和物质交换可调节细胞的生理功能和代谢水平。线粒体相关内质网膜是内质网膜和线粒体外膜之间的物理接触通道，由一系列蛋白质或蛋白质复合物形成。这种微观结构可介导多种特殊功能，如Ca2+信号传导、自噬、线粒体形态动力学、氧化应激和凋亡。而线粒体相关内质网膜介导的Ca2+信号转导紊乱是神经系统疾病发病机制的关键基础。线粒体相关内质网膜上的一些蛋白质或蛋白质复合物可直接或间接调节内质网和线粒体之间的距离以及Ca2+信号转导，且线粒体相关内质网膜介导的Ca2+信号传导会影响线粒体相关内质网膜介介导的其他功能。这些功能在缺血性脑卒中、创伤性脑损伤、阿尔茨海默病、帕金森病、肌萎缩侧索硬化、亨廷顿病等神经系统疾病发挥的作用存在一定差异。对这些神经系统疾病相关通路和功能蛋白的靶向调控常可促进受损神经元的再生和修复，进而改善神经功能。因此，线粒体相关内质网膜介导的Ca2+信号传导在神经系统疾病的病理进展中起着重要的作用，并可能成为重要的治疗靶点。此次综述重点介绍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+信号在神经系统疾病中的不同作用，即长期线粒体Ca2+超载或缺乏引起的早期保护作用和神经元损伤。文章全面分析了线粒体相关内质网膜介导的Ca2+信号传导在神经系统疾病中的不同机制，有助于进一步探索促进神经保护和神经修复的相关治疗靶点。

https://orcid.org/0000-0002-7381-9303 (Pengyue Zhang); https://orcid.org/0000-0003-3508-9132 (Jiaxin Liu)

关键词: 哺乳动物, Ca2+信号传导, 氧化应激, 线粒体动力学, 神经功能修复, 缺血性脑卒中, 创伤性脑损伤, 阿尔茨海默病, 帕金森病, 肌萎缩侧索硬化, 亨廷顿病

Abstract: 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 (Ca2+) signaling, autophagy, mitochondrial morphology, oxidative stress response, and apoptosis. Notably, the dysregulation of Ca2+ 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 Ca2+ signaling. Conversely, Ca2+ signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membraneassociated 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 Ca2+ 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 Ca2+ signaling in neurological diseases, specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca2+ overload or deficiency. This article provides a comprehensive analysis of the various mechanisms of Ca2+ 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.

Key words: Alzheimer’s disease, amyotrophic lateral sclerosis, Ca2+ signaling conduction, Huntington’s disease, ischemic stroke, mammals, mitochondrial dynamics, neural function repair, oxidative stress, Parkinson’s disease, traumatic brain injury