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論文
- タイトル
- Human tauopathy-derived tau strains determine the substrates recruited for templated amplification
- タイトル（英）
- Human tauopathy-derived tau strains determine the substrates recruited for templated amplification
- 参照URL
- https://researchmap.jp/masatohasegawa/published_papers/33625785
- 著者
- 著者（英）
- Airi Tarutani,Haruka Miyata,Takashi Nonaka,Kazuko Hasegawa,Mari Yoshida,Yuko Saito,Shigeo Murayama,Andrew C Robinson,David M A Mann,Taisuke Tomita,Masato Hasegawa
- 担当区分
- 概要
- 概要（英）
Abstract Tauopathies are a subset of neurodegenerative diseases characterized by abnormal tau inclusions. Specifically, three-repeat tau and four-repeat tau in Alzheimer’s disease, three-repeat tau in Pick’s disease (PiD) and four-repeat tau in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) form amyloid-like fibrous structures that accumulate in neurons and/or glial cells. Amplification and cell-to-cell transmission of abnormal tau based on the prion hypothesis are believed to explain the onset and progression of tauopathies. Recent studies support not only the self-propagation of abnormal tau, but also the presence of conformationally distinct tau aggregates, namely tau strains. Cryogenic electron microscopy analyses of patient-derived tau filaments have revealed disease-specific ordered tau structures. However, it remains unclear whether the ultrastructural and biochemical properties of tau strains are inherited during the amplification of abnormal tau in the brain. In this study, we investigated template-dependent amplification of tau aggregates using a cellular model of seeded aggregation. Tau strains extracted from human tauopathies caused strain-dependent accumulation of insoluble filamentous tau in SH-SY5Y cells. The seeding activity towards full-length four-repeat tau substrate was highest in CBD-tau seeds, followed by PSP-tau and Alzheimer’s disease (AD)-tau seeds, while AD-tau seeds showed higher seeding activity than PiD-tau seeds towards three-repeat tau substrate. Abnormal tau amplified in cells inherited the ultrastructural and biochemical properties of the original seeds. These results strongly suggest that the structural differences of patient-derived tau strains underlie the diversity of tauopathies, and that seeded aggregation and filament formation mimicking the pathogenesis of sporadic tauopathy can be reproduced in cultured cells. Our results indicate that the disease-specific conformation of tau aggregates determines the tau isoform substrate that is recruited for templated amplification, and also influences the prion-like seeding activity.- 出版者・発行元
- 出版者・発行元（英）
- Oxford University Press (OUP)
- 誌名
- 誌名（英）
- Brain
- 巻
- 144
- 号
- 8
- 開始ページ
- 2333
- 終了ページ
- 2348
- 出版年月
- 2021年9月4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
- 0006-8950
- DOI URL
- https://doi.org/10.1093/brain/awab091
- 共同研究・競争的資金等の研究課題
研究者
Hasegawa Masato
( )