Octyl gallate markedly promotes anti-amyloidogenic processing of APP through estrogen receptor-mediated ADAM10 activation.
PLoS One
; 8(8): e71913, 2013.
Article
em En
| MEDLINE
| ID: mdl-23977176
ABSTRACT
Our previous studies showed that the green tea-derived polyphenolic compound (-)-epigallocatechin-3 gallate (EGCG) reduces amyloid-ß (Aß) production in both neuronal and mouse Alzheimer's disease (AD) models in concert with activation of estrogen receptor-α/phosphatidylinositide 3-kinase/protein kinase B (ERα/PI3K/Akt) signaling and anti-amyloidogenic amyloid precursor protein (APP) α-secretase (a disintegrin and metallopeptidase domain-10, ADAM10) processing. Since the gallate moiety in EGCG may correspond to the 7α position of estrogen, thereby facilitating ER binding, we extensively screened the effect of other gallate containing phenolic compounds on APP anti-amyloidogenic processing. Octyl gallate (OG; 10 µM), drastically decreased Aß generation, in concert with increased APP α-proteolysis, in murine neuron-like cells transfected with human wild-type APP or "Swedish" mutant APP. OG markedly increased production of the neuroprotective amino-terminal APP cleavage product, soluble APP-α (sAPPα). In accord with our previous study, these cleavage events were associated with increased ADAM10 maturation and reduced by blockade of ERα/PI3k/Akt signaling. To validate these findings in vivo, we treated Aß-overproducing Tg2576 mice with OG daily for one week by intracerebroventricular injection and found decreased Aß levels associated with increased sAPPα. These data indicate that OG increases anti-amyloidogenic APP α-secretase processing by activation of ERα/PI3k/Akt signaling and ADAM10, suggesting that this compound may be an effective treatment for AD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Precursor de Proteína beta-Amiloide
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Receptor alfa de Estrogênio
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Proteínas ADAM
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Secretases da Proteína Precursora do Amiloide
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Doença de Alzheimer
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Ácido Gálico
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Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
PLoS One
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China