FGF21 Protects Dopaminergic Neurons in Parkinson's Disease Models Via Repression of Neuroinflammation.

Abstract

Fibroblast growth factor21 (FGF21), a member of the FGF family, plays multiple biological functions including anti-inflammation, anti-oxidative stress, and anti-apoptosis. It has been shown that FGF21 protects cells from acute injury in several kinds of cells such as islet β-cells, endothelial cells, cardiomyocytes, and dopaminergic neurons. However, whether FGF21 plays neuroprotective roles against Parkinsonian syndrome in vivo has not been elucidated. Our results showed that FGF21 markedly improves cell survival in MPP+-treated SH-SY5Y cells and primary dopaminergic neurons. Furthermore, we treated MPTP-induced Parkinson's disease (PD) model mice with the recombinant FGF21 via intranasal pathway. The results showed that FGF21 treatment significantly improves behavioral performances and prevents tyrosine hydroxylase (TH) loss in the substantia nigra par compacta (SNpc) and striatum. Mechanistically, FGF21 stimulates the AMPK/PGC-1α axis to promote mitochondrial functions. Moreover, FGF21 attenuates microglia and astrocyte activation induced by MPTP, leading to a low level of inflammation in the brain. Our data indicate that FGF21 prevents dopaminergic neuron loss and shows beneficial effects against MPTP-induced PD syndrome in mice, indicating it might be a potent candidate for developing novel drugs to deal with PD.