中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (7): 1446-1453.doi: 10.4103/1673-5374.386400

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

神经胶质细胞的神经元转分化：缺失神经元补充策略

  

  • 出版日期:2024-07-15 发布日期:2023-11-28
  • 基金资助:
    中国科学院战略重点研究计划项目（XDB39050600）；国家自然科学基金项目（81971610）；北京康复医院引进人才研究创业基金项目（2021R-008）

Neuronal conversion from glia to replenish the lost neurons

Shiyu Liang1, 2, #, Jing Zhou3, #, Xiaolin Yu1, Shuai Lu1, Ruitian Liu1, *   

  1. 1National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China; 2School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, China; 3Department of Geriatric Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
  • Online:2024-07-15 Published:2023-11-28
  • Contact: Ruitian Liu, PhD, rtliu@ipe.ac.cn.
  • Supported by:
    This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences, No. XDB39050600 (to RL); the National Natural Science Foundation of China, No. 81971610 (to RL); Beijing Rehabilitation Hospital Introduction of Talent Research Start-up Fund, No. 2021R-008 (to JZ).

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摘要：

衰老、脑血管疾病和神经退行性疾病（如脑梗死、阿尔茨海默病、帕金森病、额颞叶痴呆、肌萎缩性侧索硬化和亨廷顿舞蹈症）中可见神经元大量缺失。但是，不幸的是，包括人类在内的大多数哺乳动物中枢神经系统中的成熟神经元都无法自我再生。补充缺失的神经元已成为扭转疾病的一种潜在的治疗策略，移植多能神经干细胞虽可补充大脑中缺失的神经元，但其存在导致基因突变、肿瘤发生、严重炎症和脑水肿诱导的梗阻性脑积水方面风险。将神经细胞或非神经谱系细胞转分化为功能性神经元以治疗涉及神经元缺失的疾病，这可克服上述神经干细胞治疗的缺点。目前神经元转分化转分化主要为利用转录因子诱导星形胶质细胞、成纤维细胞、小胶质细胞、Müller神经胶质细胞、NG2胶质细胞和其他类型的神经胶质细胞转分化为成熟的功能性神经元，以及以多肽嘧啶结合蛋白1联合小分子化合物诱导神经元在不同亚型中转分化。但是最近有一些研究不能重复既往转分化的结果，使得该领域存在争议。因此文章回顾了神经元转分化的发展历史，总结了神经胶质细胞，特别是星形胶质细胞在神经元转分化方面的策略，并对相关生物安全、新策略发展以及体内转化神经元的准确示踪方面的探索进行了展望。

https://orcid.org/0000-0002-4297-4765 (Ruitian Liu)

关键词: 神经元, 转分化, 修复, 神经退行性疾病, 神经干细胞, 重编程, 星形胶质细胞, 转录因子, 多肽嘧啶结合蛋白1, 小分子

Abstract: Neuronal injury, aging, and cerebrovascular and neurodegenerative diseases such as cerebral infarction, Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Huntington’s disease are characterized by significant neuronal loss. Unfortunately, the neurons of most mammals including humans do not possess the ability to self-regenerate. Replenishment of lost neurons becomes an appealing therapeutic strategy to reverse the disease phenotype. Transplantation of pluripotent neural stem cells can supplement the missing neurons in the brain, but it carries the risk of causing gene mutation, tumorigenesis, severe inflammation, and obstructive hydrocephalus induced by brain edema. Conversion of neural or non-neural lineage cells into functional neurons is a promising strategy for the diseases involving neuron loss, which may overcome the above-mentioned disadvantages of neural stem cell therapy. Thus far, many strategies to transform astrocytes, fibroblasts, microglia, Müller glia, NG2 cells, and other glial cells to mature and functional neurons, or for the conversion between neuronal subtypes have been developed through the regulation of transcription factors, polypyrimidine tract binding protein 1 (PTBP1), and small chemical molecules or are based on a combination of several factors and the location in the central nervous system. However, some recent papers did not obtain expected results, and discrepancies exist. Therefore, in this review, we discuss the history of neuronal transdifferentiation, summarize the strategies for neuronal replenishment and conversion from glia, especially astrocytes, and point out that biosafety, new strategies, and the accurate origin of the truly converted neurons in vivo should be focused upon in future studies. It also arises the attention of replenishing the lost neurons from glia by gene therapies such as up-regulation of some transcription factors or down-regulation of PTBP1 or drug interference therapies. 

Key words: astrocytes, neural stem cells, neurodegenerative diseases, neuron, polypyrimidine tract binding protein 1, repair, reprogramming, small molecule, transcription factor, transdifferentiation