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論文
- タイトル
- タイトル（英）
- Age-dependent formation of TMEM106B amyloid filaments in human brains.
- 参照URL
- https://researchmap.jp/masatohasegawa/published_papers/36742312
- 著者
- 著者（英）
- Manuel Schweighauser,Diana Arseni,Mehtap Bacioglu,Melissa Huang,Sofia Lövestam,Yang Shi,Yang Yang,Wenjuan Zhang,Abhay Kotecha,Holly J Garringer,Ruben Vidal,Grace I Hallinan,Kathy L Newell,Airi Tarutani,Shigeo Murayama,Masayuki Miyazaki,Yuko Saito,Mari Yoshida,Kazuko Hasegawa,Tammaryn Lashley,Tamas Revesz,Gabor G Kovacs,John van Swieten,Masaki Takao,Masato Hasegawa,Bernardino Ghetti,Maria Grazia Spillantini,Benjamin Ryskeldi-Falcon,Alexey G Murzin,Michel Goedert,Sjors H W Scheres
- 担当区分
- 概要
- 概要（英）
- Many age-dependent neurodegenerative diseases, like Alzheimer's and Parkinson's, are characterised by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-β (Aβ), α-synuclein and TDP-43 are the most common1,2. Here, we used electron cryo-microscopy (cryo-EM) structure determination to show that residues 120-254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in human brains. We determined the cryo-EM structures of TMEM106B filaments from a number of brain regions of 22 individuals with abundant amyloid deposits, including sporadic and inherited tauopathies, Aβ-amyloidoses, synucleinopathies and TDP-43 proteinopathies, as well as from the frontal cortex of 3 neurologically normal individuals with no or only few amyloid deposits. We observed three TMEM106B folds, with no clear relationships between folds and diseases. TMEM106B filaments correlated with the presence of a 29 kDa sarkosyl-insoluble fragment and globular cytoplasmic inclusions, as detected by an antibody specific for the C-terminal region of TMEM106B. The identification of TMEM106B filaments in the brains of older, but not younger, neurologically normal individuals indicates that they form in an age-dependent manner.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Nature
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2022年3月28日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1038/s41586-022-04650-z
- 共同研究・競争的資金等の研究課題
研究者
Hasegawa Masato
( )