神经胶质细胞在自闭症谱系障碍中的作用:分子机制和治疗方法。

Aparna Inamdar, Bannimath Gurupadayya, Himanshu Sharma
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摘要

自闭症谱系障碍(ASD)是一种以社会沟通障碍和重复行为为特征的神经发育疾病。新出现的证据强调了神经胶质细胞,特别是星形胶质细胞和小胶质细胞在ASD病理生理中的重要作用。神经胶质细胞在维持体内平衡、调节突触功能和对神经损伤作出反应方面起着至关重要的作用。神经胶质细胞功能失调,包括细胞因子产生改变、突触修剪受损和神经炎症反应中断,与ASD有关。这些破坏的分子机制涉及异常信号通路,如mTOR通路和表观遗传修饰,导致神经胶质细胞中基因表达谱的改变。此外,小胶质细胞激活和反应性星形细胞增生导致炎症环境加剧神经回路异常。了解这些分子机制为治疗干预开辟了道路。目前针对神经胶质细胞功能障碍的治疗方法包括抗炎剂、突触功能调节剂和基于细胞的治疗。二甲胺四环素和布司特已显示出调节小胶质细胞活动和减少神经炎症的潜力。此外,基因编辑和干细胞治疗的进步有望恢复正常的神经胶质功能。这篇摘要强调了神经胶质细胞在自闭症中的重要性。这表明需要进一步研究神经胶质功能障碍与ASD发病机制之间的复杂相互作用,旨在开发能够改善ASD临床表现的靶向治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Role of Glial Cells in Autism Spectrum Disorder: Molecular Mechanisms and Therapeutic Approaches.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Emerging evidence highlights the significant role of glial cells, particularly astrocytes and microglia, in the pathophysiology of ASD. Glial cells are crucial for maintaining homeostasis, modulating synaptic function, and responding to neural injury. Dysregulation of glial cell functions, including altered cytokine production, impaired synaptic pruning, and disrupted neuroinflammatory responses, has been implicated in ASD. Molecular mechanisms underlying these disruptions involve aberrant signaling pathways, such as the mTOR pathway, and epigenetic modifications, leading to altered gene expression profiles in glial cells. Moreover, microglial activation and reactive astrocytosis contribute to an inflammatory environment that exacerbates neural circuit abnormalities. Understanding these molecular mechanisms opens avenues for therapeutic interventions. Current therapeutic approaches targeting glial cell dysfunction include anti-inflammatory agents, modulators of synaptic function, and cell-based therapies. Minocycline and ibudilast have shown potential for modulating microglial activity and reducing neuroinflammation. Additionally, advancements in gene editing and stem cell therapy hold promise for restoring normal glial function. This abstract underscores the importance of glial cells in ASD. It highlights the need for further research to elucidate the complex interactions between glial dysfunction and ASD pathogenesis, aiming to develop targeted therapies that can ameliorate the clinical manifestations of ASD.

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