Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron degeneration in adults, and several mechanisms underlying the disease pathology have been proposed. It has been shown that glia communicate with other cells by releasing extracellular vesicles containing proteins and nucleic acids, including microRNAs (miRNAs), which play a role in the post-transcriptional regulation of gene expression. Dysregulation of miRNAs is commonly observed in ALS patients, together with inflammation and an altered microglial phenotype. However, the role of miRNA-containing vesicles in microglia-to-neuron communication in the context of ALS has not been explored in depth. This review summarises the evidence for the presence of inflammation, pro-inflammatory microglia and dysregulated miRNAs in ALS, then explores how microglia may potentially be responsible for this miRNA dysregulation. The possibility of pro-inflammatory ALS microglia releasing miRNAs which may then enter neuronal cells to contribute to degeneration is also explored. Based on the literature reviewed here, microglia are a likely source of dysregulated miRNAs and potential mediators of neurodegenerative processes. Therefore, dysregulated miRNAs may be promising candidates for the development of therapeutic strategies.

中文翻译：

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活化的小胶质细胞可能是导致肌萎缩侧索硬化症神经变性的细胞外 microRNA 失调的来源。

肌萎缩侧索硬化症 (ALS) 是成人中最常见的运动神经元变性形式，并且已经提出了几种疾病病理学的机制。已经表明，神经胶质细胞通过释放含有蛋白质和核酸的细胞外囊泡与其他细胞进行交流，这些细胞外囊泡在基因表达的转录后调控中发挥作用。在 ALS 患者中通常观察到 miRNA 的失调，同时伴有炎症和小胶质细胞表型的改变。然而，在 ALS 的背景下，含 miRNA 的囊泡在小胶质细胞与神经元之间的通讯中的作用尚未得到深入探讨。本综述总结了 ALS 中存在炎症、促炎性小胶质细胞和失调 miRNA 的证据，然后探索小胶质细胞如何可能导致这种 miRNA 失调。还探讨了促炎性 ALS 小胶质细胞释放 miRNAs 的可能性，然后这些 miRNAs 可能进入神经元细胞导致退化。根据这里回顾的文献，小胶质细胞可能是失调的 miRNA 和神经退行性过程的潜在介质的来源。因此，失调的 miRNA 可能是开发治疗策略的有希望的候选者。