上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2026, Vol. 46 ›› Issue (1): 115-122.doi: 10.3969/j.issn.1674-8115.2026.01.014

• 综述 • 上一篇    

孤独症谱系障碍儿童的线粒体病理机制与靶向治疗研究进展

吴迪, 马骏()   

  1. 上海交通大学医学院附属上海儿童医学中心发育行为儿科，上海 200127
  • 收稿日期:2025-07-03 接受日期:2025-10-28 出版日期:2026-01-28 发布日期:2026-01-30
  • 通讯作者: 马　骏，主任医师，博士；电子信箱：majun@shsmu.edu.cn。
  • 作者简介:第一联系人：马骏和吴迪提出文章的思路；吴迪负责文献检索和初稿撰写；马骏参与综述撰写，负责指导并审核论文修改。所有作者均阅读并同意了最终稿件的提交。
  • 基金资助:
    上海市浦东新区卫生健康委员会项目(2025PWDL13)

Research progress on mitochondrial pathological mechanisms and targeted therapy in children with autism spectrum disorder

Wu Di, Ma Jun()   

  1. Department of Developmental and Behavioral Pediatrics, Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Received:2025-07-03 Accepted:2025-10-28 Online:2026-01-28 Published:2026-01-30
  • Contact: Ma Jun, E-mail: majun@shsmu.edu.cn.
  • About author:First author contact:LMa Jun and Wu Di proposed the idea for the article. Wu Di was responsible for literature retrieval and drafting the initial version. Ma Jun participated in manuscript writing and was responsible for guiding and reviewing the manuscript revisions. Both authors have read the final version of the paper and approved its submission.
  • Supported by:
    Project of the Health Commission of Pudong New Area, Shanghai(2025PWDL13)

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摘要：

孤独症谱系障碍（autism spectrum disorder，ASD）是儿童期起病的慢性神经发育障碍，以社交互动、沟通障碍，重复刻板行为和兴趣狭窄为核心临床表现，其病理机制涉及遗传与环境因素的交互作用，但具体生物学机制尚未完全阐明。近年研究表明，线粒体结构和功能障碍可能是ASD发病的关键环节。作为能量供应细胞器，线粒体与神经发育过程（包括神经发生、神经元迁移、突触形成及修剪等）密切相关。现有研究发现ASD患者普遍存在线粒体相关的异常改变，包括线粒体DNA变异、氧化应激水平升高及代谢紊乱等现象。机制研究表明，能量代谢缺陷、动力学失衡等线粒体功能障碍共同导致突触可塑性受损、神经环路异常，最终引发ASD核心行为表现。基于上述发现，研究者们进一步探讨了多种靶向线粒体的潜在干预策略，包括基因编辑、线粒体移植、抗氧化治疗、代谢重塑以及通过微生物组干预调节肠道-脑轴功能等方法。该文推测线粒体可能是整合遗传易感性与环境风险的关键环节之一，其结构及功能障碍不仅为ASD的神经发育异常提供生物学解释，还为未来开发针对ASD核心病理机制的干预措施指明方向。

关键词: 孤独症谱系障碍, 线粒体, 神经发育, 机制

Abstract:

Autism spectrum disorder (ASD) is a chronic neurodevelopmental disorder with onset in childhood, characterised by core clinical features including impaired social interaction and communication, as well as restricted and repetitive behaviours and interests. Its pathogenesis involves interactions between genetic and environmental factors, while the specific biological mechanisms remain incompletely elucidated. Recent studies have demonstrated that mitochondrial structural and functional disorders may be a key contributor to the pathogenesis of ASD. As the primary organelles responsible for energy production, mitochondria play a crucial role in neurodevelopmental processes, including neurogenesis, neuronal migration, synapse formation, and synaptic pruning. Current research has identified widespread mitochondrial-related abnormalities in individuals with ASD, including mitochondrial DNA mutations, elevated oxidative stress levels, and metabolic dysregulation. Mechanistic studies indicate that mitochondrial dysfunction, including energy metabolism defects and mitochondrial dynamics imbalances, collectively impair synaptic plasticity and abnormal neural circuitry, ultimately leading to the core behavioural manifestations of ASD. Based on the aforementioned findings, researchers have further explored various potential intervention strategies targeting mitochondria, including gene editing, mitochondrial transplantation, antioxidant therapy, metabolic reprogramming, and modulation of the gut-brain axis through microbiome-based interventions. This article hypothesizes that mitochondria may serve as a critical integrative hub linking genetic susceptibility and environmental risk factors. Their structural and functional dysfunctions not only provide a biological basis for the neurodevelopmental abnormalities characteristic of ASD but also point the way toward future interventions targeting the core pathophysiological mechanisms of ASD.

Key words: autism spectrum disorder (ASD), mitochondria, neurodevelopment, mechanism

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