Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (6): 1582-1598.doi: 10.4103/NRR.NRR-D-23-01872

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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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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