Improving Blood Monocyte Energy Metabolism Enhances Its Ability to Phagocytose Amyloid-β and Prevents Alzheimer's Disease-Type Pathology and Cognitive Deficits / 神经科学通报·英文版
Neuroscience Bulletin
; (6): 1775-1788, 2023.
Article
Dans En
| WPRIM
| ID: wpr-1010640
Responsable en Bibliothèque :
WPRO
ABSTRACT
Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Phagocytose
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Monocytes
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Peptides bêta-amyloïdes
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Cognition
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Métabolisme énergétique
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Maladie d'Alzheimer
Limites du sujet:
Animals
langue:
En
Texte intégral:
Neuroscience Bulletin
Année:
2023
Type:
Article