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論文
- タイトル
- Distinct tau folds initiate templated seeding and alter the post-translational modification profile
- タイトル（英）
- Distinct tau folds initiate templated seeding and alter the post-translational modification profile
- 参照URL
- https://researchmap.jp/masatohasegawa/published_papers/43715487
- 著者
- Airi Tarutani,Fuyuki Kametani,Marina Tahira,Yuko Saito,Mari Yoshida,Andrew C Robinson,David M A Mann,Shigeo Murayama,Taisuke Tomita,Masato Hasegawa
- 著者（英）
- Airi Tarutani,Fuyuki Kametani,Marina Tahira,Yuko Saito,Mari Yoshida,Andrew C Robinson,David M A Mann,Shigeo Murayama,Taisuke Tomita,Masato Hasegawa
- 担当区分
- 最終著者
- 概要
- 概要（英）
- Abstract Pathological tau accumulates in the brain in tauopathies such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration, and forms amyloid-like filaments incorporating various post-translational modifications (PTMs). Cryo-electron microscopic (cryo-EM) studies have demonstrated that tau filaments extracted from tauopathy brains are characteristic of the disease and share a common fold(s) in the same disease group. Further, the tau PTM profile changes during tau pathology formation and disease progression, and disease-specific PTMs are detected in and around the filament core. In addition, templated tau seeding has been suggested to trigger pathological tau amplification and spreading in vitro and in vivo, though the molecular mechanisms are not fully understood. Recently we reported that the cryo-EM structures of tau protofilaments in SH-SY5Y cells seeded with patient-derived tau filaments show a core structure resembling that of the original seeds. Here, we investigated PTMs of tau filaments accumulated in the seeded cells by liquid chromatography/tandem mass spectrometry and compared them with the PTMs of patient-derived tau filaments. Examination of insoluble tau extracted from SH-SY5Y cells showed that numerous phosphorylation, deamidation and oxidation sites detected in the fuzzy coat in the original seeds were well reproduced in SH-SY5Y cells. Moreover, templated tau filament formation preceded both truncation of the N-/C-terminals of tau and PTMs in and around the filament core, indicating these PTMs may predominantly be introduced after the degradation of the fuzzy coat.
- 出版者・発行元
- 出版者・発行元（英）
- Oxford University Press (OUP)
- 誌名
- Brain
- 誌名（英）
- Brain
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2023年8月10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/awad272
- 共同研究・競争的資金等の研究課題
研究者
Hasegawa Masato
( )
,
亀谷 富由樹
(カメタニ フユキ)