Oleuropein aglycone induces autophagy in neuroblastoma cells: a mechanicistic insight.

Increasing evidence points to natural polyphenols as protective tools in a wide number of human pathologies, including neurodegenerative and cardiovascular diseases, cancer and diabetes. Oleuropein aglycone (OLE), a phenol extracted from olive oil, possesses a number of properties shared with other plants polyphenols, explaining its healthy properties including the antioxidant, anti-inflammatory and anti-amyloidogenic power. Our previous data have highlighted the beneficial effects of OLE against protein/peptide aggregation in vitro and in TgCRND8 mice, a strain widely used as a model of Aβ deposition. TgCRND8 mice fed with OLE displayed improved performance in behavioural and cognitive tests, that paralleled reduced plaque load disassembly in the affected brain areas and strongly activated autophagy. The present study was aimed at investigating the molecular and cellular mechanisms of autophagy induction by OLE in cultured cells. SHSY-5Y neuroblastoma cells exposed to 50 μM OLE, showed increased autophagic vacuoles in association to a rise in cytosolic calcium, CaMKK activaction and the ensuing AMPK activation. In conclusion, our data provide evidence that the mechanism of autophagy activation by OLE implies the activation of the AMPK pathway confirming that polyphenols are useful to treat age-related diseases with autophagy dysfunction, including neurodegeneration.