Exercise and the organ-brain axis: Regulation of neurological disorders by emerging exerkines

Research on exercise and brain disorders has traditionally focused on its direct regulatory effects on neurons and synapses, neglecting peripheral organ-mediated pathways. To address this gap, this review proposes the novel concept of the "multi-organ-brain axis." This concept posits that during brain disorders, functional alterations in peripheral organs such as skeletal muscle, heart, liver, adipose tissue, and spleen can disrupt metabolic and immune homeostasis, thereby bidirectionally modulating brain function via signaling molecules and metabolites. Under this framework, we further clarify that exercise not only exerts neuroprotective effects directly in the central nervous system, but also triggers a series of peripheral adaptive responses via the "multi-organ-brain axis," including myokine secretion, adipokine spectrum reshaping, cardiac metabolic peptide release, and hepatic detoxification enhancement. These organ-level changes can cross the blood-brain barrier to improve synaptic plasticity, regulate microglia phenotypes, and optimize cerebral energy metabolism, ultimately creating an overall environment conducive to brain homeostasis.