Inamdar Aparna, Gurupadayya Bannimath, Sharma Himanshu
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Mysuru, JSS Academy of Higher Education and Research, Mysuru, 570015, India.
Department of Pharmacy, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad (UP)-244001, India.
CNS Neurol Disord Drug Targets. 2025 Jan 3. doi: 10.2174/0118715273337007241115102118.
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.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征为社交沟通缺陷和重复行为。新出现的证据凸显了胶质细胞，尤其是星形胶质细胞和小胶质细胞，在ASD病理生理学中的重要作用。胶质细胞对于维持体内平衡、调节突触功能以及对神经损伤做出反应至关重要。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紊乱，都与ASD有关。这些破坏背后的分子机制涉及异常的信号通路，如mTOR通路，以及表观遗传修饰，导致胶质细胞中基因表达谱改变。此外，小胶质细胞激活和反应性星形胶质细胞增生会导致炎症环境，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。目前针对胶质细胞功能障碍的治疗方法包括抗炎药物、突触功能调节剂和基于细胞的疗法。米诺环素和异丁司特已显示出调节小胶质细胞活性和减轻神经炎症的潜力。此外，基因编辑和干细胞治疗的进展有望恢复正常的胶质细胞功能。本摘要强调了胶质细胞在ASD中的重要性。它突出了进一步研究以阐明胶质细胞功能障碍与ASD发病机制之间复杂相互作用的必要性，旨在开发能够改善ASD临床表现的靶向治疗方法。
