The complex roles of m6A modifications in neural stem cell proliferation,differentiation,and self-renewal and implications for memory and neurodegenerative diseases
Yanxi Li
Jing Xue
Yuejia Ma
Ke Ye
Xue Zhao
Fangliang Ge
Feifei Zheng
Lulu Liu
Xu Gao
Dayong Wang
Qing Xia
Abstract：N6-methyladenosine (m6A), 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 m6A 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 m6A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m6A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m6A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m6A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m6A 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 m6A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m6A's role in neurodegenerative processes. The roles of m6A 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 time-specific nature of m6A and its varying effects on distinct brain regions and in different environments.
Keywords：Alzheimer's diseasecell self-renewalcentral nervous systemmemorymicroglianerve regenerationneurodegenerative diseasesneurogenesisRNA methylation
Publication Date：2025-06-27
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：17( 1582-1598 )