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Review

The m6A Modification in Neurodegenerative Disease: A Cellular Perspective

by
Shuowei Wang
1,2,
Ziming Feng
3,
Hongjin Wu
1,2,
Shen Wang
1,2,
Suping Qin
1,4,
Xiaotian Wang
1,4,
Feng Zhou
1,4,
Kuiyang Zheng
1,4,
Xufeng Huang
1,5,* and
Xiaomei Liu
1,4,*
1
Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou 221004, China
2
First Clinical Medical College, Xuzhou Medical University, Xuzhou 221004, China
3
School of Anesthesia, Xuzhou Medical University, Xuzhou 221004, China
4
Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou 221004, China
5
School of Medical, Indigenous, and Health Sciences, University of Wollongong, Wollongong, NSW 2522, Australia
*
Authors to whom correspondence should be addressed.
Cells 2025, 14(22), 1820; https://doi.org/10.3390/cells14221820
Submission received: 16 October 2025 / Revised: 14 November 2025 / Accepted: 18 November 2025 / Published: 20 November 2025
(This article belongs to the Section Cellular Neuroscience)
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Abstract

N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotes and plays a critical role in gene expression regulation by influencing RNA stability, splicing, nuclear export, and translation. Emerging evidence suggests that dysregulation of m6A contributes to neuroinflammation, neurotoxicity, and synaptic dysfunction—key features of neurodegenerative diseases. This review aims to examine the role of m6A modification in neurodegenerative diseases from a cell-type-specific perspective. We systematically reviewed recent studies investigating m6A modifications in neurons and glial cells. Data from transcriptomic, epitranscriptomic, and functional studies were analyzed to understand how m6A dynamics influence disease-related processes. Findings indicate that m6A modifications regulate neuroinflammation and immune responses in microglia, modulate astrocytic support functions, affect myelination through oligodendrocytes, and alter m6A patterns in neurons, impacting synaptic plasticity, stress responses, and neuronal survival. These cell-type-specific roles of m6A contribute to the progression of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic lateral sclerosis (ALS). Understanding m6A-modulated mechanisms in specific neural cell types may facilitate the development of targeted interventions for neurodegenerative diseases.
Keywords: m6A; glial cells; neuron; neurodegenerative diseases m6A; glial cells; neuron; neurodegenerative diseases

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MDPI and ACS Style

Wang, S.; Feng, Z.; Wu, H.; Wang, S.; Qin, S.; Wang, X.; Zhou, F.; Zheng, K.; Huang, X.; Liu, X. The m6A Modification in Neurodegenerative Disease: A Cellular Perspective. Cells 2025, 14, 1820. https://doi.org/10.3390/cells14221820

AMA Style

Wang S, Feng Z, Wu H, Wang S, Qin S, Wang X, Zhou F, Zheng K, Huang X, Liu X. The m6A Modification in Neurodegenerative Disease: A Cellular Perspective. Cells. 2025; 14(22):1820. https://doi.org/10.3390/cells14221820

Chicago/Turabian Style

Wang, Shuowei, Ziming Feng, Hongjin Wu, Shen Wang, Suping Qin, Xiaotian Wang, Feng Zhou, Kuiyang Zheng, Xufeng Huang, and Xiaomei Liu. 2025. "The m6A Modification in Neurodegenerative Disease: A Cellular Perspective" Cells 14, no. 22: 1820. https://doi.org/10.3390/cells14221820

APA Style

Wang, S., Feng, Z., Wu, H., Wang, S., Qin, S., Wang, X., Zhou, F., Zheng, K., Huang, X., & Liu, X. (2025). The m6A Modification in Neurodegenerative Disease: A Cellular Perspective. Cells, 14(22), 1820. https://doi.org/10.3390/cells14221820

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