Muscle-brain endocrine axis in autism spectrum disorder: Mechanisms, evidence, and research priorities

Figure 2 Hypothesis-generating translational framework for staged exercise research in autism spectrum disorder. Phase 1 distinguishes currently feasible clinical and behavioral inputs from emerging or research-only stratification measures. Phase 2 depicts proposed exercise-responsive muscle and systemic pathways, with biomarkers labeled as candidate research measures and recombinant or small-molecule approaches as investigational targets. Phase 3 shows potential combinations with behavioral therapy, neuromodulation, and pharmacotherapy; direct synergistic efficacy remains to be established. IL: Interleukin; BDNF: Brain-derived neurotrophic factor; TrkB: Tropomyosin receptor kinase B; PGC-1α: Peroxisome proliferator-activated receptor γ coactivator-1α; HPA: Hypothalamic-pituitary-adrenal; ABA: Applied behavior analysis; CBT: Cognitive behavioral therapy; PMC: Premotor cortex; HPC: Hippocampus; PFC: Prefrontal cortex; FNDC5: Fibronectin type III domain-containing protein 5; STAT3: Signal transducer and activator of transcription 3; AMPK: AMP-activated protein kinase; MCTs: Monocarboxylate transporters; Akt: Protein kinase B; IGF-1: Insulin-like growth factor 1; PI3K: Phosphoinositide 3-kinase; CRH: Corticotropin-releasing hormone; ACTH: Adrenocorticotropic hormone; rTMS: Repetitive transcranial magnetic stimulation; tDCS: Transcranial direct current stimulation.