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論文
- タイトル
- タイトル（英）
- Phosphorylation of α-synuclein at T64 results in distinct oligomers and exerts toxicity in models of Parkinson's disease.
- 参照URL
- https://researchmap.jp/masatohasegawa/published_papers/43170547
- 著者
- 著者（英）
- Hideaki Matsui,Shinji Ito,Hideki Matsui,Junko Ito,Ramil Gabdulkhaev,Mika Hirose,Tomoyuki Yamanaka,Akihide Koyama,Taisuke Kato,Maiko Tanaka,Norihito Uemura,Noriko Matsui,Sachiko Hirokawa,Maki Yoshihama,Aki Shimozawa,Shin-Ichiro Kubo,Kenji Iwasaki,Masato Hasegawa,Ryosuke Takahashi,Keisuke Hirai,Akiyoshi Kakita,Osamu Onodera
- 担当区分
- 概要
- 概要（英）
- α-Synuclein accumulates in Lewy bodies, and this accumulation is a pathological hallmark of Parkinson's disease (PD). Previous studies have indicated a causal role of α-synuclein in the pathogenesis of PD. However, the molecular and cellular mechanisms of α-synuclein toxicity remain elusive. Here, we describe a novel phosphorylation site of α-synuclein at T64 and the detailed characteristics of this post-translational modification. T64 phosphorylation was enhanced in both PD models and human PD brains. T64D phosphomimetic mutation led to distinct oligomer formation, and the structure of the oligomer was similar to that of α-synuclein oligomer with A53T mutation. Such phosphomimetic mutation induced mitochondrial dysfunction, lysosomal disorder, and cell death in cells and neurodegeneration in vivo, indicating a pathogenic role of α-synuclein phosphorylation at T64 in PD.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Proceedings of the National Academy of Sciences of the United States of America
- 巻
- 120
- 号
- 23
- 開始ページ
- e2214652120
- 終了ページ
- 出版年月
- 2023年6月6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/10.1073/pnas.2214652120
- 共同研究・競争的資金等の研究課題
研究者
Hasegawa Masato
( )