Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined, neurodevelopmental disorder that has been modeled as a brain-based disease. The behavioral and cognitive features of ASD are associated with pervasive atypicalities in the central nervous system (CNS). To date, the exact mechanisms underlying the pathophysiology of ASD still remain unknown and there is currently no cure or effective treatment for this disorder. Many publications implicated the association of ASD with inflammation, immune dysregulation, neurotransmission dysfunction, mitochondrial impairment and cell signaling dysregulation. This review attempts to highlight evidence of the major pathophysiology of ASD including abnormalities in the brain structure and function, neuroglial activation and neuroinflammation, glutamatergic neurotransmission, mitochondrial dysfunction and mechanistic target of rapamycin (mTOR) signaling pathway dysregulation. Molecular and cellular factors that contributed to the pathogenesis of ASD and how they may affect the development and function of CNS are compiled in this review. However, findings of published studies have been complicated by the fact that autism is a very heterogeneous disorder; hence, we addressed the limitations that led to discrepancies in the reported findings. This review emphasizes the need for future studies to control study variables such as sample size, gender, age range and intelligence quotient (IQ), all of which that could affect the study measurements. Neuroinflammation or immune dysregulation, microglial activation, genetically linked neurotransmission, mitochondrial dysfunctions and mTOR signaling pathway could be the primary targets for treating and preventing ASD. Further research is required to better understand the molecular causes and how they may contribute to the pathophysiology of ASD.

中文翻译：

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自闭症谱系障碍中枢神经系统的非典型性更新。

自闭症谱系障碍（ASD）是一种异质的，行为定义的神经发育障碍，已被建模为基于脑的疾病。ASD的行为和认知特征与中枢神经系统（CNS）普遍存在的非典型性有关。迄今为止，ASD病理生理学的确切机制仍不清楚，目前尚无治愈或有效治疗该疾病的方法。许多出版物暗示ASD与炎症，免疫失调，神经传递功能障碍，线粒体损伤和细胞信号传导失调有关。这篇评论试图强调ASD的主要病理生理学证据，包括脑结构和功能异常，神经胶质激活和神经炎症，谷氨酸能神经传递，雷帕霉素（mTOR）信号通路异常的线粒体功能障碍和机制靶点。本文综述了导致ASD发病机理的分子和细胞因素，以及它们如何影响CNS的发育和功能。然而，由于自闭症是一种非常异质的疾病，已发表的研究结果变得复杂。因此，我们解决了导致报告结果差异的局限性。这篇评论强调未来的研究需要控制研究变量，例如样本量，性别，年龄范围和智商（IQ），所有这些因素都可能影响研究测量。神经炎症或免疫功能异常，小胶质细胞激活，遗传相关的神经传递，线粒体功能障碍和mTOR信号通路可能是治疗和预防ASD的主要靶标。需要进一步研究以更好地了解分子原因以及它们如何对ASD的病理生理产生影响。