Microglial complement receptor 3 regulates brain Aß levels through secreted proteolytic activity.
J Exp Med
; 214(4): 1081-1092, 2017 04 03.
Article
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| MEDLINE
| ID: mdl-28298456
ABSTRACT
Recent genetic evidence supports a link between microglia and the complement system in Alzheimer's disease (AD). In this study, we uncovered a novel role for the microglial complement receptor 3 (CR3) in the regulation of soluble ß-amyloid (Aß) clearance independent of phagocytosis. Unexpectedly, ablation of CR3 in human amyloid precursor protein-transgenic mice results in decreased, rather than increased, Aß accumulation. In line with these findings, cultured microglia lacking CR3 are more efficient than wild-type cells at degrading extracellular Aß by secreting enzymatic factors, including tissue plasminogen activator. Furthermore, a small molecule modulator of CR3 reduces soluble Aß levels and Aß half-life in brain interstitial fluid (ISF), as measured by in vivo microdialysis. These results suggest that CR3 limits Aß clearance from the ISF, illustrating a novel role for CR3 and microglia in brain Aß metabolism and defining a potential new therapeutic target in AD.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Péptidos beta-Amiloides
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Antígeno de Macrófago-1
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Microglía
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Año:
2017
Tipo del documento:
Article