自闭症谱系障碍的神经炎症机制和药理学进展：从炎症途径到靶向干预
Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions.
摘要(中文译文)
孤独症谱系障碍（ASD）在病因和症状上具有高度异质性，目前仍缺乏可靠的生物标志物和基于机制的治疗靶点。神经炎症已被认为与ASD风险、症状发展及长期病程相关，但其关键的“体—脑”联系及实际干预切入点尚未得到清晰梳理。我们综合了临床免疫与脑脊液研究、神经影像学、动物模型及多组学研究证据，沿循从孕期母体免疫激活（MIA）到出生后免疫失衡、炎症信号向大脑传递以及中枢神经系统内后续放大的机制路径进行阐述。我们提出“外周—中枢炎症级联放大模型”（PC-ICAM），以总结可干预节点及近期药理学进展。在PC-ICAM框架内，ASD相关神经炎症遵循从外周免疫扰动到外周—中枢传递再到中枢放大的级联过程。外周信号可能通过血脑屏障（BBB）脆弱性、细胞外囊泡/miRNA通讯及神经免疫调节通路影响中枢神经系统。涉及NF-κB、JAK/STAT、MAPK/ERK、NLRP3及PI3K-AKT-mTOR的炎症信号可能与微胶质细胞和星形胶质细胞激活、氧化应激及线粒体功能障碍汇聚，扰乱突触稳态与兴奋—抑制平衡。候选干预措施靶向IL-6/IL-17信号、炎症通路、炎症小体活性、胶质细胞调节、抗氧化/线粒体支持、BBB稳定、微生物群相关免疫调节及外泌体-miRNA通路。PC-ICAM将ASD相关神经炎症界定为一条可追踪、可干预且具有放大效应的外周—中枢级联，提供了结构化的机制图谱与治疗机会。该模型提示，精准治疗不应依赖单一抗炎策略，而应沿级联路径采用多节点、机制匹配的联合干预。
Abstract
Autism spectrum disorder (ASD) is highly diverse in causes and symptoms, and reliable biomarkers and mechanism-based treatment targets are still lacking. Neuroinflammation has been linked to ASD risk, symptom development, and long-term course, but the key "body-to-brain" connections and practical intervention points are not yet clearly organized. We synthesize evidence from clinical immune and cerebrospinal fluid studies, neuroimaging, animal models, and multi-omics research, following a mechanistic path from maternal immune activation (MIA) during pregnancy to postnatal immune imbalance, transmission of inflammatory signals to the brain, and subsequent amplification within the central nervous system. We propose the Peripheral-to-Central Inflammatory Cascade-Amplification Model (PC-ICAM) to summarize actionable nodes and recent pharmacological advances. Within PC-ICAM, ASD-related neuroinflammation follows a cascade from peripheral immune perturbation to peripheral-to-central transmission and central amplification. Peripheral signals may affect the CNS through BBB vulnerability, extracellular vesicle/miRNA communication, and neuro-immune regulatory pathways. Inflammatory signaling involving NF-κB, JAK/STAT, MAPK/ERK, NLRP3, and PI3K-AKT-mTOR may converge with microglial and astrocytic activation, oxidative stress, and mitochondrial dysfunction, disturbing synaptic homeostasis and excitation-inhibition balance. Candidate interventions target IL-6/IL-17 signaling, inflammatory pathways, inflammasome activity, glial modulation, antioxidant/mitochondrial support, BBB stabilization, microbiota-related immune modulation, and exosome-miRNA pathways. PC-ICAM frames ASD-related neuroinflammation as a traceable and actionable peripheral-to-central cascade with amplification, providing a structured map of mechanisms and therapeutic opportunities. It suggests that precision treatment should not rely on a single anti-inflammatory strategy, but rather combine multi-node, mechanism-matched interventions along the cascade.
如何引用
AMA
Xinyu Zhang, Huiqin Xue, Chaoyang Zhu, Chen Ji, Yin Li, Wei Liu. Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1829127.
APA
Xinyu Zhang, Huiqin Xue, Chaoyang Zhu, Chen Ji, Yin Li, Wei Liu (2026). Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1829127
GB/T 7714
Xinyu Zhang, Huiqin Xue, Chaoyang Zhu, Chen Ji, Yin Li, Wei Liu. Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1829127.
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