The healthy effects of plant polyphenols, some of which characterize the so-called Mediterranean diet, have been shown to arise from epigenetic and biological modifications resulting, among others, in autophagy stimulation. Our previous work highlighted the beneficial effects of oleuropein aglycone (OLE), the main polyphenol found in the extra virgin olive oil, against neurodegeneration both in cultured cells and in model organisms, focusing, in particular, autophagy activation. In this study we investigated the molecular and cellular mechanisms of autophagy induction by OLE using cultured neuroblastoma cells and a mouse model of Aβ deposition. We found that OLE triggers autophagy both in cultured cells and in the animal model through the Ca2+-CaMKKβ-AMPK-mTOR axis. In particular, in cultured cells OLE induces a rapid release of Ca2+ from the ER stores which, in turn, activates CaMKKβ, with subsequent phosphorylation and activation of AMPK, inhibition of mTOR and autophagy ignition. Our results agree with those reported for other plant polyphenols, suggesting a shared molecular mechanism underlying the healthy effects of these substances against ageing, neurodegeneration, cancer, diabetes and other diseases implying autophagy dysfunction.

Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: A mechanistic insight / Rigacci, Stefania; Miceli, Caterina; Nediani, Chiara; Berti, Andrea; Cascella, Roberta; Pantano, Daniela; Nardiello, Pamela; Luccarini, Ilaria; Casamenti, Fiorella; Stefani, Massimo. - In: ONCOTARGET. - ISSN 1949-2553. - ELETTRONICO. - 6:(2015), pp. 35344-35357. [10.18632/oncotarget.6119]

Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: A mechanistic insight

RIGACCI, STEFANIA;MICELI, CATERINA;NEDIANI, CHIARA;BERTI, ANDREA;CASCELLA, ROBERTA;PANTANO, DANIELA;NARDIELLO, PAMELA;LUCCARINI, ILARIA;CASAMENTI, FIORELLA;STEFANI, MASSIMO
2015

Abstract

The healthy effects of plant polyphenols, some of which characterize the so-called Mediterranean diet, have been shown to arise from epigenetic and biological modifications resulting, among others, in autophagy stimulation. Our previous work highlighted the beneficial effects of oleuropein aglycone (OLE), the main polyphenol found in the extra virgin olive oil, against neurodegeneration both in cultured cells and in model organisms, focusing, in particular, autophagy activation. In this study we investigated the molecular and cellular mechanisms of autophagy induction by OLE using cultured neuroblastoma cells and a mouse model of Aβ deposition. We found that OLE triggers autophagy both in cultured cells and in the animal model through the Ca2+-CaMKKβ-AMPK-mTOR axis. In particular, in cultured cells OLE induces a rapid release of Ca2+ from the ER stores which, in turn, activates CaMKKβ, with subsequent phosphorylation and activation of AMPK, inhibition of mTOR and autophagy ignition. Our results agree with those reported for other plant polyphenols, suggesting a shared molecular mechanism underlying the healthy effects of these substances against ageing, neurodegeneration, cancer, diabetes and other diseases implying autophagy dysfunction.
2015
6
35344
35357
Rigacci, Stefania; Miceli, Caterina; Nediani, Chiara; Berti, Andrea; Cascella, Roberta; Pantano, Daniela; Nardiello, Pamela; Luccarini, Ilaria; Casamenti, Fiorella; Stefani, Massimo
File in questo prodotto:
File Dimensione Formato  
Oncotarget 2015.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 8.19 MB
Formato Adobe PDF
8.19 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1041708
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 105
  • ???jsp.display-item.citation.isi??? 100
social impact