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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
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食塩はタウリン酸化によって認知障害を助長する
Giuseppe Faraco1, Karin Hochrainer2, Steven G Segarra2
1Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. gif2004@med.cornell.edu.
Nature
|October 25, 2019
まとめ
過剰な食塩摂取は,タウタンパク質の高酸化を促すことで,マウスの認知機能低下を引き起こします. 窒素酸化物の生成を回復させたり,タウを遮断することは,塩,血管の健康,神経変性との関係を強調します.
科学分野:
- 神経科学
- 血管生物学
- ダイエット 科学
背景:
- アルツハイマー病と血管性認知障害には 食事習慣と血管性リスク要因が関係しています
- アルツハイマー病の特徴である高酸化タウも 血管性認知障害と関連しています
- 塩分が多い食事は ネズミに窒素酸化物の欠乏と脳低血流による 認知機能障害を引き起こします
研究 の 目的:
- 食塩,内皮機能障害,および認知障害におけるタウ病理の因果関係を調査する.
- 塩によって引き起こされる認知機能の低下に 窒素酸化物の生成が 重要かどうかを判断する
- 血液動力学的要因とは無関係に塩による認知障害におけるタウの役割を調査する.
主な方法:
- マウスに塩分豊富な食事を与え 認知機能を評価した
- 脳内皮細胞の窒素酸化物産生を測定した.
- タウのリン酸化,カルパインのニトロシル化,およびサイクリン依存キナーゼ5の活性を調べた.
- タウの作用を評価するためにタウゼロマウスと抗タウ抗体を用いた.
主要な成果:
- ダイエット塩はマウスでタウの高酸化と認知機能障害を誘発した.
- これらの効果は,内皮の酸化窒素の生成を回復することによって防ぐことができました.
- 窒素酸化物の欠乏はカルパインの活性化と,その後のタウリン酸化を引き起こした.
- 塩による認知障害は,継続的な低血流にもかかわらず,タウゼロのマウスおよび抗タウ抗体で治療されたマウスには存在しなかった.
結論:
- 食塩は,内皮の酸化窒素欠乏によって直接,タウ病変と認知障害を誘発する.
- この発見は,高い塩分摂取量,血管機能障害,および脳血流の減少とは無関係なタオパシーとの間の因果関係を確立しています.
- 血管の健康を維持し 過剰な塩分摂取を避けることは 年齢に関連した認知機能低下や 認知症の予防に不可欠です
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