FNDC5/Irisin protects neurons through Caspase3 and Bax pathways

Irisin is a glycosylated protein formed from the hydrolysis of fibronectin type III domain-containing protein 5 (FNDC5). Recent studies have demonstrated that FNDC5/Irisin is involved in the regulation of glucose and lipid metabolism, it can inhibit inflammation and have neuroprotective effects. However, the effect and mechanism of FNDC5/Irisin on motor neuron-like cell lines (NSC-34) have not been reported. In this study, we used lipopolysaccharide to construct cellular oxidative stress injury models and investigated the potential roles of FNDC5/Irisin on neurons by different cellular and molecular pathways. Taken together, our findings showed that FNDC5/Irisin can protect neurons, and this effect might be associated with Caspase3 and Bax pathways. These results laid the foundation for neuronal protection and clinical translation of FNDC5/Irisin therapy. Neuronal injury can lead to severe neurological dysfunction and it brings a heavy medical burden to families and society. FNDC5/Irisin is an exercise-induced glycosylated protein, and it is unclear whether FNDC5/Irisin has a protective effect on neurons. In the current study, lipopolysaccharide-induced motor neuron-like cell lines (NSC-34) were used, and we found that FNDC5/Irisin increased the levels of mitochondrial antioxidants and decreased the apoptosis in NSC-34 cells. FNDC5/Irisin can protect neurons through Caspase3 and Bax pathways.