Fibroblast growth factor-21 alleviates proteasome injury via activation of autophagy flux in Parkinson's disease

Parkinson's disease (PD) is one of the most common and complex Neurodegeneration, with an inherited metabolic disorder. Fibroblast Growth Factor 21 (FGF21), an endocrine hormone that belongs to the Fibroblast Growth Factor superfamily, plays an extensive role in metabolic regulation. However, our understandings of the specific function and mechanisms of FGF21 on PD are still quite limited. Here, we aimed to elucidate the actions and the underlying mechanisms of FGF21 on dopaminergic neurodegeneration using cellular models of parkinsonism. To investigate the effects of FGF21 on dopaminergic neurodegeneration in vitro, Proteasome impairment models of PD were utilized. Human dopaminergic neuroblastoma SH-SY5Y cells were treated with the Proteasome Inhibitor lactacystin (5 μmol/L) for 12 h, then with 50 ng/ml FGF-21 with or without 5 mmol/L of 3-methyladenine.The cells were dissected to assess alterations in Autophagy using immunofluorescence, immunoblotting and electron microscopy assays. Our data indicate that FGF21 prevents dopaminergic neuron loss and shows beneficial effects against Proteasome impairment induced PD syndrome, indicating it might be a potent candidate for developing novel drugs to deal with PD.

Autophagy; Fibroblast growth factor 21; Neurodegeneration; Parkinson’s disease; Proteasome; Ubiquitin–proteasome system.