An Aß42 uptake and degradation via Rg3 requires an activation of caveolin, clathrin and Aß-degrading enzymes in microglia.
Eur J Pharmacol
; 758: 1-10, 2015 07 05.
Article
en En
| MEDLINE
| ID: mdl-25848967
ABSTRACT
We demonstrated previously that ginsenoside Rg3 enhances the expression of macrophage scavenger receptor class A (SRA) and amyloid ß peptide 1-42 (Aß42) uptake in BV2 cells. In this study, we investigated the biochemical and mechanistic roles of Rg3 in human microglia and animal models to identify the determinants that participate in restoring memory and learning in brains disrupted by the Aß42 peptide. SRA was expressed highly in Rg3-treated rats, and learning and memory functions were maintained at a normal level after the infusion of Aß42. SRA-transfected HMO6 human microglial cells (HMO6.hSRA) overexpressed SRA and took up a remarkable amount of Aß42. Rg3-treated HMO6 cells showed highly enhanced SRA expression and dramatically promoted Aß42 uptake. Moreover, high levels of clathrin and caveolin1 supported the roles of Rg3 in endocytic biogenesis by activating p38 and extracellular signal-regulated protein kinase signaling. Notably, both neprilysin (NEP) and insulin-degrading enzyme (IDE) were significantly expressed by Rg3, suggesting independent and compensatory hydrolytic activity for the Aß peptide. In conclusion, Rg3 successfully triggered Aß42 uptake via SRA and clathrin-/caveolae-mediated endocytic mechanisms and further contributed to accelerate the degradation of Aß peptide via the increase of intracellular NEP and IDE, which may be a promising Alzheimer׳s disease therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Clatrina
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Microglía
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Ginsenósidos
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Caveolina 1
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Insulisina
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2015
Tipo del documento:
Article