LAUSR

Significance Physical exercise is thought to have beneficial effects on the symptoms of Parkinson’s disease (PD). Irisin is an exercise-induced myokine released into the circulation. We therefore tested whether irisin itself could have a beneficial effect on pathologic α-synuclein (α-syn) accumulation and concomitant neurodegeneration in PD. Here, we show that irisin prevents the accumulation of pathologic α-syn and neuronal cell death by enhancing endolysosomal degradation of pathologic α-syn. Furthermore, elevation of blood irisin levels in mice prevented neurodegeneration and physiological deficits induced by injection α-syn preformed fibrils. These findings would seem to have translational promise as a disease-modifying therapy for treating PD and other neurodegenerative diseases involving pathologic α-syn.