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論文
タイトル
タイトル(英)
Volatile Anesthetic Sevoflurane Precursor 1,1,1,3,3,3-Hexafluoro-2-Propanol (HFIP) Exerts an Anti-Prion Activity in Prion-Infected Culture Cells
参照URL
https://researchmap.jp/alz42/published_papers/32800770
著者
著者(英)
Takuto Shimizu,Emiko Nogami,Yuka Ito,Kazuo Morikawa,Masaki Nagane,Tadashi Yamashita,Tsuyoshi Ogawa,Fuyuki Kametani,Hisashi Yagi,Naomi Hachiya
概要
概要(英)
AbstractPrion disease is a neurodegenerative disorder with progressive neurologic symptoms and accelerated cognitive decline. The causative protein of prion disease is the prion protein (PrP), and structural transition of PrP from the normal helix rich form (PrPC) to the abnormal β-sheet rich form (PrPSc) occurs in prion disease. While so far numerous therapeutic agents for prion diseases have been developed, none of them are still useful. A fluorinated alcohol, hexafluoro isopropanol (HFIP), is a precursor to the inhalational anesthetic sevoflurane and its metabolites. HFIP is also known as a robust α-helix inducer and is widely used as a solvent for highly aggregated peptides. Here we show that the α-helix-inducing activity of HFIP caused the conformational transformation of the fibrous structure of PrP into amorphous aggregates in vitro. HFIP added to the ScN2a cell medium, which continuously expresses PrPSc, reduced PrPSc protease resistance after 24-h incubation. It was also clarified that ScN2a cells are more susceptible to HFIP than any of the cells being compared. Based on these findings, HFIP is expected to develop as a therapeutic agent for prion disease.
出版者・発行元
出版者・発行元(英)
Springer Science and Business Media LLC
誌名
誌名(英)
Neurochemical Research
開始ページ
終了ページ
出版年月
2021年5月27日
査読の有無
査読有り
招待の有無
掲載種別
研究論文(学術雑誌)
ISSN
0364-3190
DOI URL
https://doi.org/10.1007/s11064-021-03344-8
共同研究・競争的資金等の研究課題
研究者
亀谷 富由樹 (カメタニ フユキ)