中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (3): 972-988.doi: 10.4103/NRR.NRR-D-24-01054

• 综述:退行性病与再生 • 上一篇    下一篇

多种神经退行性疾病的潜在共同发病机制

  

  • 出版日期:2026-03-15 发布日期:2025-07-02
  • 基金资助:
    本研究得到国家自然科学基金(82160255);江西省自然科学基金(20212BAB216026);江西省卫生计生委科技计划项目(202110016);江西省中医药管理局科技计划项目(2022B975);江西省重点实验室基金(202110016);江西省中医药管理局科技计划项目(2022B97);江西省神经病学重点实验室基金(2024SSY06081)。

Potential common pathogenesis of several neurodegenerative diseases

Ting Fan1, 2, #, Jiaman Peng1, 2, #, Huiting Liang3, #, Wenzhi Chen1, #, Junlin Wang1 , Renshi Xu1, 2, *   

  1. 1 Department of Neurology, Jiangxi Provincial People’s Hospital; The Clinical College of Nanchang Medical College; The First Affiliated Hospital of Nanchang Medical College; Xiangya Hospital of Center South University, Jiangxi Hospital; National Regional Center for Neurological Disease, Nanchang, Jiangxi Province, China; 2 Medical College of Nanchang University, Nanchang, Jiangxi Province, China; 3 Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
  • Online:2026-03-15 Published:2025-07-02
  • Contact: Renshi Xu, MD, PhD, xurenshi@ncu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82160255 (to RX); the Natural Science Foundation of Jiangxi Province, No. 20212BAB216026 (to HL); Science and Technology Plan Project of Health Commission of Jiangxi Province, No. 202110016 (to HL); Science and Technology Plan Project of Jiangxi Provincial Administration of Traditional Chinese Medicine, No. 2022B975 (to HL); and a grant from Jiangxi Province Key Laboratory of Neurology, No. 2024SSY06081 (to RX)

摘要:

随着研究方法和技术的不断进步,人们发现多种生物学过程参与了神经退行性疾病的发病机制,但目前发现的与神经退行性疾病发病机制相关的生物学过程并不能完全阐明神经退行性疾病的发病、进展和发展过程。因此,继续探索神经退行性疾病的发病机制是一项非常有价值的研究。在这篇综述中,作者利用概述了阿尔茨海默病、帕金森病、肌萎缩侧索硬化、亨廷顿病、额颞叶痴呆以及路易体病的潜在共同发病机制。结果表明,此6种神经退行性疾病发病机制中可能涉及的共同生物过程包括老龄化、遗传、进行性神经元功能障碍/死亡/凋亡、蛋白质错误折叠、聚集和构象、蛋白质聚集的传播、神经炎症、线粒体功能障碍、轴突运输缺陷以及肠道微生物群/菌群失调。这些致病机制在6种神经退行性疾病中存在一定的交叉和相互关系,直接或间接地诱发或发展了 神经退行性疾病。根据目前来自各方面的研究信息,作者认为这些生物过程可能构建了复杂的致病网络,在神经退行性疾病的发病机制中引发了独特的神经元死亡,如果这些神经退行性疾病的发病机制能够被预防或逆转,那么这些受损神经元的再生可能会通过修复受损的神经细胞(包括神经元)而得到促进。总之,这些潜在的共同生物过程可能只是一个非常小的、有限的元素,在复杂网络中的无数致病因素中起着很小的靶向作用,因为在临床治疗中,干扰任何一个单一的生物过程都不能完全阻止这些神经退行性疾病的进展。因此,未来对神经退行性疾病发病机制的研究方向应侧重于寻找神经退行性疾病发病机制中的复杂致病网络,而不是寻找单一的生物学过程。在此基础上,通过阻止或逆转神经退行性疾病潜在发病机制中的各种靶点来进行靶向治疗可能是一个值得期待的方向,因为目前所有应用阻止神经退行性疾病某个唯一致病靶点的治疗方法都没有取得令人满意的疗效。

https://orcid.org/0000-0003-0313-3434 (Renshi Xu)

关键词: 阿尔茨海默病, 帕金森病, 肌萎缩侧索硬化症, 亨廷顿病, 额颞叶痴呆症, 路易体病, 老龄化, 遗传学, 进行性神经元功能障碍, 蛋白质错误折叠

Abstract: With the gradual advancement of research methods and technologies, various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases. However, current descriptions of these biological processes do not fully explain the onset, progression, and development of these conditions. Therefore, exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research. This review summarizes the potential common pathogeneses of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, frontotemporal lobar dementia, and Lewy body disease. Research findings have indicated that several common biological processes, including aging, genetic factors, progressive neuronal dysfunction, neuronal death and apoptosis, protein misfolding and aggregation, neuroinflammation, mitochondrial dysfunction, axonal transport defects, and gut microbiota dysbiosis, are involved in the pathogenesis of these six neurodegenerative diseases. Based on current information derived from diverse areas of research, these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases. Furthermore, promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed. Hence, these potential common biological processes may represent only very small, limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases. In clinical treatment, interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases. Therefore, future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks, rather than isolating individual biological processes. Based on this, therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions, as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.

Key words: aging, Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal lobar dementia, genetics, Huntington’s disease, Lewy body disease, Parkinson’s disease, progressive neuron dysfunction and death, protein misfolding