Neuromodulatory role and therapeutic potential of N6-methyladenosine RNA methylation in neurodegenerative diseases

作者：Jinyu Zhang, Wenjing Ma, Ranxu Liu, Xiaoheng Li, Zengqiang Yuan, Jinbo Cheng · 发表于：Neural Regeneration Research · 年份：2025 · DOI：10.4103/nrr.nrr-d-24-01648 · 被引用次数：6 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Cancer-related gene regulation

N 6 -methyladenosine RNA methylation, an essential post-transcriptional modification, dynamically regulates RNA metabolism and plays a crucial role in neuronal function. Growing evidence suggests that dysregulated N 6 -methyladenosine modification contributes to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. However, the precise mechanisms by which N 6 -methyladenosine modification influences these conditions remain unclear. This review summarizes the role of m 6 A modification and its associated regulators in neurodegeneration, focusing on their involvement in key pathological processes. In Alzheimer's disease, m 6 A modification contributes to synaptic dysfunction, mitochondrial damage, and neuronal apoptosis. Evidence from APP/PS1, 5xFAD, tau transgenic, and Drosophila models demonstrates that regulators such as methyltransferase-like 3 and fat mass and obesity-associated protein influence Alzheimer's disease progression through neuroinflammation, circular RNAs dysregulation, and autophagy-related mechanisms. In Parkinson's disease, altered N 6 -methyladenosine regulator expression affects dopaminergic neuron survival and stress responses by modulating mRNA stability and autophagy-related lncRNAs. In multiple sclerosis and amyotrophic lateral sclerosis, N 6 -methyladenosine affects immune activation, myelin repair, and the regulation of disease-associated genes such ...