2021年9月24日
Alzheimer's Aβ assembly binds sodium pump and blocks endothelial NOS activity via ROS-PKC pathway in brain vascular endothelial cells.
iScience
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- 巻
- 24
- 号
- 9
- 開始ページ
- 102936
- 終了ページ
- 102936
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.isci.2021.102936
Amyloid β-protein (Aβ) may contribute to worsening of Alzheimer's disease (AD) through vascular dysfunction, but the molecular mechanism involved is unknown. Using ex vivo blood vessels and primary endothelial cells from human brain microvessels, we show that patient-derived Aβ assemblies, termed amylospheroids (ASPD), exist on the microvascular surface in patients' brains and inhibit vasorelaxation through binding to the α3 subunit of sodium, potassium-ATPase (NAKα3) in caveolae on endothelial cells. Interestingly, NAKα3 is also the toxic target of ASPD in neurons. ASPD-NAKα3 interaction elicits neurodegeneration through calcium overload in neurons, while the same interaction suppresses vasorelaxation by increasing the inactive form of endothelial nitric oxide synthase (eNOS) in endothelial cells via mitochondrial ROS and protein kinase C, independently of the physiological relaxation system. Thus, ASPD may contribute to both neuronal and vascular pathologies through binding to NAKα3. Therefore, blocking the ASPD-NAKα3 interaction may be a useful target for AD therapy.
- リンク情報
- ID情報
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- DOI : 10.1016/j.isci.2021.102936
- PubMed ID : 34458695
- PubMed Central 記事ID : PMC8379508