Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions
5 affiliations
- 1Children’s Hospital, Tianjin University
- 2Medical School, Tianjin University
- 3Department of Research and Education, Tianjin Children’s Hospital
- 4Rare Diseases Medical Center, Tianjin Children’s Hospital
- 5Tianjin Key Laboratory of Birth Defects for Prevention and Treatment
Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
Related
- Mechanisms of inflammatory cell activation in periodontitis-induced bone destruction and advances in targeted interventions
- Past, present, and future of non-pharmacological interventions for autism spectrum disorder: A global bibliometric and thematic analysis (2001-2025).
- Effectiveness of non-pharmacological interventions on stress and anxiety management in pregnancy: a systematic review
- Phytochemical Profiling and Safety Assessment of Maerua crassifolia Forssk. Aerial Parts Infusion With Pharmacological Validation of Its Analgesic and Anti‐Inflammatory Activities
- The NPIS model: a consensus-based framework for evaluating non-pharmacological interventions
BibTeX
@article{zhang2026neuroinflammatory,
title = {{Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions}},
author = {Xinyu Zhang and Huiqin Xue and Chaoyang Zhu and Chen Ji and Y M Li and W.T. Liu},
journal = {Frontiers in Immunology},
year = {2026},
month = may,
doi = {10.3389/fimmu.2026.1829127},
url = {https://doi.org/10.3389/fimmu.2026.1829127},
note = {CC BY},
}
RIS
TY - JOUR
TI - Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions
AU - Xinyu Zhang
AU - Huiqin Xue
AU - Chaoyang Zhu
AU - Chen Ji
AU - Y M Li
AU - W.T. Liu
PY - 2026
DA - 2026/05/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1829127
UR - https://doi.org/10.3389/fimmu.2026.1829127
AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
SN - 1664-3224
ER -