1. Nesfatin-1 protects dopaminergic neurons against MPP + /MPTP-induced neurotoxicity through the C-Raf-ERK1/2-dependent anti-apoptotic pathway.
- Author
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Shen XL, Song N, Du XX, Li Y, Xie JX, and Jiang H
- Subjects
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolism, 1-Methyl-4-phenylpyridinium metabolism, Animals, Caspase 3 metabolism, Cells, Cultured, Cytochromes c metabolism, Disease Models, Animal, Dopaminergic Neurons physiology, MAP Kinase Signaling System, Mice, Nucleobindins, Apoptosis, Calcium-Binding Proteins metabolism, DNA-Binding Proteins metabolism, Dopaminergic Neurons drug effects, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Nerve Tissue Proteins metabolism, Parkinson Disease pathology, Proto-Oncogene Proteins c-raf metabolism
- Abstract
Several brain-gut peptides have been reported to have a close relationship with the central dopaminergic system; one such brain-gut peptide is nesfatin-1. Nesfatin-1 is a satiety peptide that is predominantly secreted by X/A-like endocrine cells in the gastric glands, where ghrelin is also secreted. We previously reported that ghrelin exerted neuroprotective effects on nigral dopaminergic neurons, which implied a role for ghrelin in Parkinson's disease (PD). In the present study, we aim to clarify whether nesfatin-1 has similar effects on dopaminergic neurons both in vivo and in vitro. We show that nesfatin-1 attenuates the loss of nigral dopaminergic neurons in the 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. In addition, nesfatin-1 antagonized 1-methyl-4-phenylpyridillium ion (MPP
+ )-induced toxicity by restoring mitochondrial function, inhibiting cytochrome C release and preventing caspase-3 activation in MPP+ -treated MES23.5 dopaminergic cells. These neuroprotective effects could be abolished by selective inhibition of C-Raf and the extracellular signal-regulated protein kinase 1/2 (ERK1/2). Our data suggest that C-Raf-ERK1/2, which is involved in an anti-apoptotic pathway, is responsible for the neuroprotective effects of nesfatin-1 in the context of MPTP-induced toxicity. These results imply that nesfatin-1 might have therapeutic potential for PD.- Published
- 2017
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