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.

Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates / Luccarini I; Grossi C; Rigacci S; Coppi E; Pugliese A.M.; Pantano D.; la Marca G; Ed Dami T; Berti A.; Stefani M.; Casamenti F. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - ELETTRONICO. - 36:(2015), pp. 648-663. [10.1016/j.neurobiolaging.2014.08.029]

Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates

LUCCARINI, ILARIA;GROSSI, CRISTINA;RIGACCI, STEFANIA;COPPI, ELISABETTA;PUGLIESE, ANNA MARIA;PANTANO, DANIELA;LA MARCA, GIANCARLO;ED DAMI, TERESA;BERTI, ANDREA;STEFANI, MASSIMO;CASAMENTI, FIORELLA
2015

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.
2015
36
648
663
Luccarini I; Grossi C; Rigacci S; Coppi E; Pugliese A.M.; Pantano D.; la Marca G; Ed Dami T; Berti A.; Stefani M.; Casamenti F
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/968350
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