Chu Aimee J, Williams Joanna M
Department of Anatomy, Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
Front Physiol. 2022 Feb 10;12:826697. doi: 10.3389/fphys.2021.826697. eCollection 2021.
Astrocytes actively regulate numerous cell types both within and outside of the central nervous system in health and disease. Indeed, astrocyte morphology, gene expression and function, alongside the content of astrocyte-derived extracellular vesicles (ADEVs), is significantly altered by ageing, inflammatory processes and in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Here, we review the relevant emerging literature focussed on perturbation in expression of microRNA (miRNA), small non-coding RNAs that potently regulate gene expression. Synthesis of this literature shows that ageing-related processes, neurodegenerative disease-associated mutations or peptides and cytokines induce dysregulated expression of miRNA in astrocytes and in some cases can lead to selective incorporation of miRNA into ADEVs. Analysis of the miRNA targets shows that the resulting downstream consequences of alterations to levels of miRNA include release of cytokines, chronic activation of the immune response, increased apoptosis, and compromised cellular functioning of both astrocytes and ADEV-ingesting cells. We conclude that perturbation of these functions likely exacerbates mechanisms leading to neuropathology and ultimately contributes to the cognitive or motor symptoms of neurodegenerative diseases. This field requires comprehensive miRNA expression profiling of both astrocytes and ADEVs to fully understand the effect of perturbed astrocytic miRNA expression in ageing and neurodegenerative disease.
在健康和疾病状态下，星形胶质细胞积极调节中枢神经系统内外的多种细胞类型。事实上，随着年龄增长、炎症过程以及在神经退行性疾病（如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症）中，星形胶质细胞的形态、基因表达和功能，以及星形胶质细胞衍生的细胞外囊泡（ADEVs）的内容物都会发生显著改变。在这里，我们综述了相关的新兴文献，重点关注微小RNA（miRNA）表达的扰动，微小RNA是一种能有效调节基因表达的小非编码RNA。对这些文献的综合分析表明，与衰老相关的过程、神经退行性疾病相关的突变或肽以及细胞因子会诱导星形胶质细胞中miRNA表达失调，在某些情况下还会导致miRNA选择性地掺入ADEVs。对miRNA靶标的分析表明，miRNA水平改变所产生的下游后果包括细胞因子的释放、免疫反应的慢性激活、细胞凋亡增加以及星形胶质细胞和摄取ADEVs的细胞的细胞功能受损。我们得出结论，这些功能的扰动可能会加剧导致神经病理学的机制，并最终导致神经退行性疾病的认知或运动症状。该领域需要对星形胶质细胞和ADEVs进行全面的miRNA表达谱分析，以充分了解衰老和神经退行性疾病中星形胶质细胞miRNA表达扰动的影响。
