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Neuroscience ; 362: 70-78, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-28844000

RESUMO

Amyloid-ß (Aß) production and clearance in the brain is a crucial focus of investigations into the pathogenesis of Alzheimer disease. Imbalance between production and clearance leads to accumulation of Aß. The important Aß-degrading enzymes in the brain are neprilysin (NEP) and insulin-degrading enzyme (IDE), and defective enzyme expression may facilitate Aß deposition in sporadic late-onset AD patients. It has been suggested that epigallocatechin gallate (EGCG), a member of the catechin family, might be an effective treatment for AD, because it has been shown to elevate NEP expression. Therefore, we examined whether catechins, which are functional components of common foods, could regulate the degradation of Aß by inducing NEP and IDE expression. We also investigated the role of catechins in activating intracellular signal transduction in astrocytes. Treatment of cultured rat astrocytes with EGCG significantly reduced the expression of NEP, but not IDE, in a concentration- and time-dependent manner. NEP expression in cultured astrocytes was suppressed by activation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K), and reduced NEP expression was accompanied by an increase of NEP release into the extracellular space (culture medium). Moreover, culture medium from EGCG-treated astrocytes facilitated the degradation of exogenous Aß. These results suggest that EGCG may have a beneficial effect on AD by activating ERK-and PI3K-mediated pathways in astrocytes, thus increasing astrocyte secretion of NEP and facilitating degradation of Aß.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Astrócitos/efeitos dos fármacos , Catequina/análogos & derivados , Neprilisina/metabolismo , Fármacos Neuroprotetores/farmacologia , Animais , Astrócitos/enzimologia , Astrócitos/metabolismo , Catequina/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Córtex Cerebral/metabolismo , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Isoflavonas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteólise/efeitos dos fármacos , Ratos Sprague-Dawley
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