Irisin promotes autophagy and attenuates NLRP3 inflammasome activation in Parkinson's disease

Parkinson's disease (PD) is characterized by the aggregation and prion-like propagation of alpha-synuclein (alpha-syn). Irisin is an exercise-induced myokine that regulates energy metabolism and exerts protective effects in PD by reducing alpha-syn pathology. However, the molecular mechanisms underlying the role of irisin are not fully understood. Here, we show that irisin inhibits NLRP3 inflammasome activation and promotes autophagy in cultured cells. Additionally, irisin alleviates oxidative stress and reduces cell apoptosis induced by alpha-syn fibrils. In a PD mouse model induced by intrastriatal injection of alpha-syn fibrils, irisin mitigated alpha-syn aggregation, neuroinflammation and neurodegeneration. These observations suggest that irisin functions as a protective mediator against alpha-syn pathology in PD and that irisin may serve as a potential therapeutic target for the prevention and treatment of PD.