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Published on: January 7, 2014
FGF21 Protects Dopaminergic Neurons in Parkinson's Disease Models Via Repression of Neuroinflammation
Xingxing Fang1, Jinyu Ma2, Dengcai Mu3
1Department of Nephrology, the Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
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.
Insights
Fibroblast growth factor 21 (FGF21) protects against Parkinson's disease by preserving dopaminergic neurons and reducing brain inflammation. This study suggests FGF21 as a potential therapeutic candidate for Parkinson's disease treatment.
Area of Science:
- Neuroscience
- Molecular Biology
- Endocrinology
Background:
- Fibroblast growth factor 21 (FGF21) is known for its roles in metabolism and protection against cellular injury.
- Its neuroprotective effects, particularly in Parkinsonian syndromes, remain largely uninvestigated in vivo.
Purpose of the Study:
- To investigate the potential neuroprotective effects of FGF21 against Parkinson's disease (PD) models.
- To elucidate the underlying mechanisms of FGF21's action in dopaminergic neurodegeneration.
Main Methods:
- In vitro studies using MPP+-treated SH-SY5Y cells and primary dopaminergic neurons.
- In vivo studies using MPTP-induced Parkinson's disease mouse models treated with intranasal FGF21.
- Assessment of behavioral changes, dopaminergic neuron survival (tyrosine hydroxylase staining), inflammatory markers, and mitochondrial function (AMPK/PGC-1α axis).
Main Results:
- FGF21 significantly enhanced survival of dopaminergic neurons in vitro.
- Intranasal FGF21 administration improved motor behavior and prevented dopaminergic neuron loss in MPTP-treated mice.
- FGF21 treatment activated the AMPK/PGC-1α pathway, improved mitochondrial function, and reduced neuroinflammation by attenuating microglia and astrocyte activation.
Conclusions:
- FGF21 demonstrates significant neuroprotective effects in both in vitro and in vivo models of Parkinson's disease.
- FGF21 mitigates dopaminergic neurodegeneration by enhancing mitochondrial function and suppressing neuroinflammation.
- FGF21 represents a promising therapeutic candidate for the development of novel treatments for Parkinson's disease.
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