title: Edaravone prevents neurotoxicity of mutant L166P DJ-1 in Parkinson's disease.
abstract: Parkinson's disease (PD), which is estimated to affect approximately 1 % of the population over the age of 65, is the second most common neurodegenerative disorder after Alzheimer's disease. It was reported that pathogenic mutations in DJ-1 lead to autosomal recessive early-onset familial Parkinsonism. The L166P mutant of DJ-1 is the most commonly studied loss-of-function mutation in early onset familial PD, but the underlying mechanisms are still unknown. Edaravone is a powerful free radical scavenger used in clinical treatment for cerebral ischemic stroke. In the present study, we investigated the effects of edaravone on the neurotoxicity in PD-induced isoforms of DJ-1 containing the mutation L166P. Our results indicated that edaravone was able to significantly attenuate oxidative stress and improve mitochondrial function. Furthermore, edaravone was found to reduce apoptosis in Neuro2a cells through modulation of mitochondria-dependent apoptosis pathways. Interestingly, our result also demonstrated that edaravone was able to up-regulate VMAT2 expression in N2a cells in a dose-dependent manner. Our findings enhance the understanding of the neuro-protective effects of edaravone in cell models and suggest that edaravone offers significant protection in a PD-related in vitro model.
authors: Department of Neurology, Yantai Yuhuangding Hospital of Medical College of Qingdao University, Yantai, Shandong, 264000, People's Republic of China, yingbing6699@yahoo.com.cn.
authors: Bing
authors: B
authors: Li
authors: Dawei
authors: D
authors: Yu
authors: Zhiying
authors: Z
authors: Xu
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000235:genetics; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D015513:Oncogene Proteins; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D000077553:Edaravone; D000983:Antipyrine
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