Investigation on antioxidants with low pro-oxidant activity to stabilize proteins responsible for neurodegenerative disease.

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14723
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Bioorganic chemistry
• Research Institution: Fukui Prefectural University
• Principal Investigator: KUROKAWA Yoichi 福井県立大学, 生物資源学部, 講師 (40326088)
• Co-Investigator(Renkei-kenkyūsha): OHIGASHI Hajime 福井県立大学, 生物資源学部, 名誉教授 (80026583) ; KANO Kenji 京都大学, 農学研究科, 教授 (10152828) ; IRIE Kazuhiro 京都大学, (連合)農学研究科, 教授 (00168535) ; YAMANAKA Koji 名古屋大学, 環境医学研究所, 教授 (80446533)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 抗酸化能 / プロオキシダント能 / 銅イオン還元能 / ヒドロキシルラジカル / スーパーオキシドディスムターゼ 1 / 蛋白質変性

Outline of Final Research Achievements

We aimed in this research to explore antioxidants such prevent oxidative denaturation of proteins which are causative of certain neurodegenerative disease, such as familial amyotrophic lateral sclerosis (fALS). For this purpose, we first chose antioxidants that have low pro-oxidant activity, an ability to generate hydroxyl radical via copper-induced oxidation. We then investigated anti-oxidant activity of compounds with low pro-oxidant activity by measuring their ability to inhibit chemical luminescence of luminol or to protect inactivation of glucose- 6-phosphate dehydrogenase under an oxidative condition such generates hydroxyl radical, finding that several flavonoids including methylated flavones have such ability. When we examined the alleviation effects of compounds on toxicity in Neuro 2a cells expressing fALS SOD1 mutant, some sesquiterpene was found as effective one. Finally, polymethoxyflavonoids were found to have partially prevent the oxidative denaturation of SOD1 protein.

Free Research Field

生化学