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論文
- タイトル
- タイトル（英）
- α-Synuclein V15A Variant in Familial Parkinson's Disease Exhibits a Weaker Lipid-Binding Property.
- 参照URL
- https://researchmap.jp/4686ss/published_papers/39577168
- 著者
- 著者（英）
- Kensuke Daida,Shotaro Shimonaka,Kahori Shiba-Fukushima,Jun Ogata,Hiroyo Yoshino,Ayami Okuzumi,Taku Hatano,Yumiko Motoi,Tomoki Hirunagi,Masahisa Katsuno,Hideo Shindou,Manabu Funayama,Kenya Nishioka,Nobutaka Hattori,Yuzuru Imai
- 担当区分
- 概要
- 概要（英）
- BACKGROUND: The α-Synuclein (α-Syn) V15A variant has been found in two Caucasian families with Parkinson's disease (PD). However, the significance of this missense variant remained unclear. OBJECTIVE: We sought to elucidate whether V15A could increase aggregation or change phospholipid affinity. METHODS: A sequencing analysis for the SNCA encoding α-Syn from 875 patients with PD and 324 control subjects was performed. Comparing with known pathogenic missense variants of α-Syn, A30P, and A53T, we analyzed the effects of V15A on binding to phospholipid membrane, self-aggregation, and seed-dependent aggregation in cultured cells. RESULTS: Genetic screening identified SNCA c.44 T>C (p.V15A) from two Japanese PD families. The missense variant V15A was extremely rare in several public databases and predicted as pathogenic using in silico tools. The amplification activity of α-Syn V15A fibrils was stronger than that of wild-type α-Syn fibrils. CONCLUSIONS: The discovery of the V15A variant from Japanese families reinforces the possibility that the V15A variant may be a causative variant for developing PD. V15A had a reduced affinity for phospholipids and increased propagation activity compared with wild-type. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Movement disorders : official journal of the Movement Disorder Society
- 巻
- 37
- 号
- 10
- 開始ページ
- 2075
- 終了ページ
- 2085
- 出版年月
- 2022年7月27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/10.1002/mds.29162
- 共同研究・競争的資金等の研究課題
研究者
下中 翔太郎
(シモナカ ショウタロウ)