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 (6): 1582-1598.doi: 10.4103/NRR.NRR-D-23-01872

• 综述:退行性病与再生 • 上一篇    下一篇

m6A修饰在神经干细胞、记忆和神经退行性疾病中的复杂作用

  

  • 出版日期:2025-06-15 发布日期:2024-11-10

The complex roles of m6A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

Yanxi Li1, 2, #, Jing Xue1, 2, #, Yuejia Ma1, 2, #, Ke Ye1, 2, Xue Zhao1, 2, Fangliang Ge1, 2, Feifei Zheng1, 2, Lulu Liu1, 2, Xu Gao1, 2, 3, 4, 5, #br# Dayong Wang1, 2, 5, *, Qing Xia6, *#br#   

  1. t of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang Province, China;  2 College of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang Province, China;  3 Basic Medical Institute, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang Province, China;  4 Key Laboratory of Heilongjiang Province for Genetically Modified Animals, Harbin Medical University, Harbin, Heilongjiang Province, China;  5 Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang Province, China; 6 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
  • Online:2025-06-15 Published:2024-11-10
  • Contact: Dayong Wang, PhD, wangdayonghmu@126.com; Qing Xia, PhD, j1995y@126.com.
  • Supported by:
    This work was supported by the Natural Science Foundation of Heilongjiang Province of China, Outstanding Youth Foundation, No. YQ2022H003 (to DW).

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摘要：

N6-甲基腺苷(m6A)是真核细胞中最普遍和广泛保留的RNA变化形式，对几乎所有mRNA代谢过程都有影响。mRNA高度浓集并与神经干细胞生成和神经再生过程密切相关。m6A修饰水平及其相关酶蛋白表达水平可引起神经功能障碍并导致神经系统疾病。与此同时，神经干细胞的增殖、分化以及神经再生与记忆和神经退行性疾病密切相关。为此，文章探讨了m6A在神经干细胞、记忆以及神经退行性疾病中的作用发现：①m6A对神经干细胞的增殖和分化表现出分歧效应，这可能是由于m6A在不同阶段起作用并对神经干细胞产生不同的影响，表明m6A具有时间特异性。②m6A对不同类型的记忆产生不同的影响，这可能由于不同的脑区控制不同类型的记忆，在不同的脑区中，m6A的作用也不同导致。③最后，在神经退行性疾病中存在一些矛盾的结果，尤其是阿尔茨海默病和帕金森病，在不同的阿尔茨海默病模型中，m6A水平的变化是不同的，这表明这些差异可能来自于模型过程中涉及的不同脑区的变化；与正常帕金森病模型相比，锰暴露的帕金森病模型中m6A水平的变化与之相反。④总之，m6A修饰在神经干细胞、记忆和神经退行性疾病中的出现一些矛盾效应，这种矛盾可能是由于m6A具有时间特异性、在不同脑区作用差异和不同环境中产生的不同效应所致。

https://orcid.org/0000-0002-9672-3347 (Dayong Wang); https://orcid.org/0000-0002-0506-9977 (Qing Xia)


关键词:

"> 阿尔茨海默病, 细胞自我更新, 中枢神经系统, 记忆, 小胶质细胞, 神经再生, 神经退行性疾病, 神经发生, m6A

Abstract: N6-methyladenosine (m6 A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m6 A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m6 A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m6 A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m6 A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m6 A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m6 A levels across different models of neurodegenerative disease, particularly Alzheimer’s disease and Parkinson’s disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m6 A levels observed in Parkinson’s disease models exposed to manganese compared to normal Parkinson’s disease models further underscore the complexity of m6 A’s role in neurodegenerative processes. The roles of m6 A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m6 A and its varying effects on distinct brain regions and in different environments

Key words: Alzheimer’s disease, cell self-renewal, central nervous system, memory, microglia, nerve regeneration, neurodegenerative diseases, neurogenesis, RNA methylation