Oleuropein Aglycone: A Possible Drug against Degenerative Conditions. In Vivo Evidence of its Effectiveness against Alzheimer's Disease

The amyloid plaques and neurofibrillary tangles found in the Alzheimer's disease (AD) brain arise as a result of self-assembly into fibrillar material of amyloid-β protein (Aβ) and hyperphosphorylated tau, respectively, through a pathological process starting with the appearance of aggregation nuclei and neurotoxic oligomers. Accordingly, the search of inhibitors of oligomer nucleation and growth is considered a promising target to prevent amyloid toxicity. In recent years, a number of dietary factors including antioxidants, vitamins, and polyphenols have been characterized for their ability to protect cells stressed by several factors including the presence of amyloid deposits as well as to inhibit amyloid self-assembly and cytotoxicity and some of them are currently in clinical trial. The present review summarizes the findings on the beneficial effects against neurodegeneration and other peripheral inflammatory and degenerative diseases of oleuropein aglycone (OLE), a natural phenol abundant in the extra virgin olive oil. The data presently available suggest that OLE could provide a protective and therapeutic effect against a number of pathologies, including AD as well as obesity, type 2 diabetes, non-alcoholic hepatitis, and other natural or experimentally-induced pathological conditions. Such a protection could result, at least in part, in a remarkable improvement of the pathological signs arising from stress conditions including oxidative stress, an excessive inflammatory response, and the presence of cytotoxic aggregated material. In particular, the recent data on the cellular and molecular correlates of OLE neuroprotection suggest it could also play a therapeutic role against AD.