Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates.
Neurobiol Aging
; 36(2): 648-63, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25293421
ABSTRACT
Amyloid-ß (Aß) fragments, oligomeric Aß aggregates, and pyroglutamylated-Aß peptides, as well as epigenetic mechanisms and autophagy dysfunction all appear to contribute in various ways to Alzheimer's disease progression. We previously showed that dietary supplementation of oleuropein aglycone, a natural phenol abundant in the extra virgin olive oil, can be protective by reducing Aß42 deposits in the brain of young and middle-aged TgCRND8 mice. Here, we extended our study to aged TgCRND8 mice showing increased pE3-Aß in the brain deposits. We report that oleuropein aglycone is active against glutaminylcyclase-catalyzed pE3-Aß generation reducing enzyme expression and interferes both with Aß42 and pE3-Aß aggregation. Moreover, the phenol astonishingly activates neuronal autophagy even in mice at advanced stage of pathology, where it increases histone 3 and 4 acetylation, which matches both a decrease of histone deacetylase 2 expression and a significant improvement of synaptic function. The occurrence of these functional, epigenetic, and histopathologic beneficial effects even at a late stage of the pathology suggests that the phenol could be beneficial at the therapeutic, in addition to the prevention, level.
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Base de dados:
MEDLINE
Métodos Terapêuticos e Terapias MTCI:
Terapias_biologicas
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Aromoterapia
Assunto principal:
Fragmentos de Peptídeos
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Encéfalo
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Peptídeos beta-Amiloides
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Iridoides
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Epigênese Genética
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Doença de Alzheimer
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Agregados Proteicos
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Itália