Amyotrophic lateral sclerosis (ALS) is a progressive neurogenerative disorder with uncertain origins. Emerging evidence implicates N6-methyladenosine (m⁶A) modification in ALS pathogenesis. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and liquid chromatography–mass spectrometry were utilized for m⁶A profiling in peripheral immune cells and serum proteome analysis, respectively, in patients with ALS (n = 16) and controls (n = 6). The single-cell transcriptomic dataset (GSE174332) of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes. Analysis of peripheral immune cells revealed extensive RNA hypermethylation, highlighting candidate genes with differential m⁶A modification and expression, including C-X3-C motif chemokine receptor 1 (CX3CR1). In RAW264.7 macrophages, disrupted CX3CR1 signaling affected chemotaxis, potentially influencing immune cell migration in ALS. Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS. Cell type-specific expression variations of these genes in the central nervous system (CNS), particularly microglia, were observed. Intercellular communication between neurons and glial cells was selectively altered in ALS CNS. This integrated approach underscores m⁶A dysregulation in immune cells as a potential ALS contributor.

肌萎缩侧索硬化症（ALS）是一种起源不确定的进行性神经再生障碍。新出现的证据表明 N6-甲基腺苷 (m ⁶ A) 修饰与 ALS 发病机制有关。甲基化 RNA 免疫沉淀测序 (MeRIP-seq) 和液相色谱-质谱法分别用于 ALS 患者 ( n = 16) 和对照组 ( n = 6)的外周免疫细胞 m ^{6 A 分析和血清蛋白质组分析。}进一步分析初级运动皮层的单细胞转录组数据集 (GSE174332)，以阐明差异甲基化基因和细胞通讯变化的生物学意义。外周免疫细胞分析揭示了广泛的 RNA 高甲基化，突出显示了具有差异 m ⁶ A 修饰和表达的候选基因，包括 C-X3-C 基序趋化因子受体 1 (CX3CR1)。在 RAW264.7 巨噬细胞中，CX3CR1 信号传导中断会影响趋化性，从而可能影响 ALS 中的免疫细胞迁移。血清蛋白质组分析证明了免疫细胞迁移失调在 ALS 中的作用。观察到这些基因在中枢神经系统（CNS），特别是小胶质细胞中的细胞类型特异性表达变化。在 ALS 中枢神经系统中，神经元和神经胶质细胞之间的细胞间通讯发生选择性改变。这种综合方法强调了免疫细胞中 m ⁶ A 失调是 ALS 的潜在贡献者。