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Effects of gem-dihydroperoxides against mutant copper‑zinc superoxide dismutase-mediated neurotoxicity
https://gifu-pu.repo.nii.ac.jp/records/13463
https://gifu-pu.repo.nii.ac.jp/records/1346360acad66-0a5f-4816-bced-e52ee211d582
| Item type | 研究室原著論文(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-03-04 | |||||
| タイトル | ||||||
| タイトル | Effects of gem-dihydroperoxides against mutant copper‑zinc superoxide dismutase-mediated neurotoxicity | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 抄録 | ||||||
| 値 | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis, and death. Although its neuropathol. is well investigated, currently, effective treatments are unavailable. The mechanism of ALS involves the aggregation and accumulation of several mutant proteins, including mutant copper-zinc superoxide dismutase (SOD1), TAR DNA binding protein 43 kDa (TDP-43) and fused in sarcoma (FUS) proteins. Previous reports have shown that excessive oxidative stress, assocd. with mitochondrial dysfunction and mutant protein accumulation, contributes to ALS pathol. The present study focuses on the promotion of SOD1 misfolding and aggregation by oxidative stress. Having recently synthesized novel org. gem-dihydroperoxides (DHPs) with high anti-oxidant activity, we now examd. whether DHPs reduce the mutant SOD1-induced intracellular aggregates involved in oxidative stress. We found that, among DHPs, 12AC2O significantly inhibited mutant SOD1-induced cell death and reduced the intracellular mutant SOD1 aggregates. Moreover, immunofluorescence staining with redox-sensitive dyes showed that 12AC2O reduced the excessive level of intracellular mutant SOD1-induced reactive oxygen species (ROS). Addnl., ESR anal. showed that 12AC2O exerts a direct scavenging effect against the hydroxyl radical (·OH) and the superoxide anion (O2-). These results suggest that 12AC2O is a very useful agent in combination with other agents against ALS. | |||||
| 書誌情報 |
en : Molecular and Cellular Neuroscience 巻 92, p. 177-184, 発行日 2018 |
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| DOI | ||||||
| 値 | 10.1016/j.mcn.2018.09.001 | |||||
