Irisin/PGC-1α/FNDC5 pathway in Parkinson's disease: truth under the throes

Parkinson's disease (PD) is considered one of the most common neurodegenerative brain diseases which involves the deposition of alpha-synuclein. Irisin hormone, a newly discovered adipokine, has a valuable role in diverse neurodegenerative diseases. Therefore, this review aims to elucidate the possible role of the irisin hormone in PD neuropathology. Irisin hormone has a neuroprotective effect against the development and progression of various neurodegenerative disorders by increasing the expression of brain-derived neurotrophic factor (BDNF). Irisin hormone has anti-inflammatory, anti-apoptotic, and anti-oxidative impacts, thereby reducing the expression of the pro-inflammatory cytokines and the progression of neuroinflammation. Irisin-induced PGC-1 alpha could potentially prevent alpha-synuclein-induced dopaminergic injury, neuroinflammation, and neurotoxicity in PD. Inhibition of NF-kappa B by irisin improves PGC-1 alpha and FNDC5 signaling pathway with subsequent attenuation of PD neuropathology. Therefore, the irisin/PGC-1 alpha/FNDC5 pathway could prevent dopaminergic neuronal injury. In conclusion, the irisin hormone has a neuroprotective effect through its anti-inflammatory and antioxidant impacts with the amelioration of brain BDNF levels. Further preclinical and clinical studies are recommended in this regard.