title: Nesfatin-1 protects dopaminergic neurons against MPP+/MPTP-induced neurotoxicity through the C-Raf-ERK1/2-dependent anti-apoptotic pathway.
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.
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Shen
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Song
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
authors.forename: Xi-Xun
authors.initials: XX
authors.lastname: Du
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Xie
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism; D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology; D020935:MAP Kinase Signaling System; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000080866:Nucleobindins; D010300:Parkinson Disease / Q000473:pathology*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D045304:Cytochromes c; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019908:Proto-Oncogene Proteins c-raf; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium