This review synthesizes evidence that m6A RNA methylation dynamically regulates neuronal plasticity, is reconfigured with aging, and is implicated across neurodegenerative diseases including Parkinson's via effects on dopaminergic and glutamatergic signaling, synaptic integrity, inflammation, and…

It identifies actionable molecular targets and biomarker directions (m6A enzymes/readers linked to dopaminergic vulnerability and synaptic dysfunction) that could open novel therapeutic or diagnostic paths for Parkinson's, although most data remain correlative and require causal, cell-type-specific…

m6A is a pervasive post-transcriptional RNA modification that regulates RNA splicing, stability, localization, and translation in the brain. In this review, we outline the core m6A regulatory machinery and summarize its spatial organization across neurons and glial cells, highlighting established roles in brain development, synapse formation, and axon growth. We then focus on experience-dependent plasticity, synthesizing evidence that neuronal activity and environmental inputs dynamically reshape m6A to regulate immediate-early transcription and local translation at synapses across sensory, cognitive, emotional, and motor domains. With aging, m6A programs are reconfigured in a cell-type-specific manner, a shift associated with reduced plasticity and increased vulnerability. We further survey disease-associated alterations in m6A across Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke-related cognitive impairment, ALS and FTD, as well as metal or toxin exposure, emphasizing convergent effects on dopaminergic and glutamatergic signaling, synaptic integrity, inflammation, and cellular stress responses. Finally, we discuss emerging opportunities and conceptual challenges in targeting m6A enzymes or reader proteins, and outline priorities for future work, including cell-type- and subcellular-resolved mapping, causal perturbation in defined circuits and life stages, and the development of biomarkers and selective modulators. Together, these observations position m6A as a molecular interface linking experience-dependent plasticity, brain aging, and neurodegenerative vulnerability.