The m6A Modification in Neurodegenerative Disease: A Cellular Perspective.

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.