Irisin, the muscle-derived hormone released during exercise, delivers direct neuroprotection in a mouse model of multiple sclerosis. Researchers delivered it peripherally and saw improved clinical scores, less neuronal loss across spinal cord, hippocampus, and retina, plus preserved synapses and mitochondrial function. It crossed the blood-brain barrier, bound motor neurons through upregulated αVβ5 integrin, and activated neuroprotective genes without touching immune pathways. Cognitive performance rose as a result. This separates the exercise benefit from immunomodulation and points to a targeted way to address MS neurodegeneration. One related human trial showed aerobic exercise raised serum irisin while improving motor and cognitive metrics in RRMS patients. The mechanism looks actionable for follow-on work thanks @EricTopol