Abstract
Alzheimer's disease is a proteinopathy characterized by accumulation of hyperphosphorylated Tau and β-amyloid. Autophagy is a physiological process by which aggregated proteins and damaged organelles are eliminated through lysosomal digestion. Autophagy deficiency has been demonstrated in Alzheimer's patients impairing effective elimination of aggregates and damaged mitochondria, leading to their accumulation, increasing their toxicity and oxidative stress. In the present study, we demonstrated by microarray analysis the downregulation of fundamental autophagy and mitophagy pathways in Alzheimer's patients. The benefits of the Mediterranean diet on Alzheimer's disease and cognitive impairment are well known, attributing this effect to several polyphenols, such as oleuropein aglycone (OLE), present in extra virgin olive oil. OLE is able to induce autophagy, achieving a decrease of aggregated proteins and a reduction of cognitive impairment in vivo. This effect is caused by the modulation of several pathways including the AMPK/mTOR axis and the activation of autophagy gene expression mediated by sirtuins and histone acetylation or EB transcription factor. We propose that supplementation of diet with extra virgin olive oil might have potential benefits for Alzheimer's patients by the induction of autophagy by OLE.
Highlights
We propose that supplementation of diet with extra virgin olive oil might have potential benefits for Alzheimer’s patients by the induction of autophagy by oleuropein aglycone (OLE)
We have focused our attention in OLE, one of the polyphenols abundant in extra virgin olive oil (EVOO) and one of the bases of the Mediterranean diet [94]
We have summarized all the works that have demonstrated that OLE reduced symptoms of Alzheimer’s disease (AD) and cognitive impairment [68, 70, 71, 89]
Summary
There are several adaptor proteins that recognize cargo to be engulfed into autophagosomes such as p62 (sequestosome 1), Next to BRCA1 gene 1 protein (NBR1), Nuclear Domain 10 Protein 52 (NDP52; known as CALCOCO2), and optineurin These proteins recognize substrates labeled for degradation by ubiquitination, for example, and bind to LC3 family proteins of phagosome mediating the recruitment of cargoes [15]. As a consequence of age and oxidative stress, the efficacy of this system is reduced This results in the accumulation of poorly digested proteins in autophagic vacuoles and damaged mitochondria, which cause an increase in oxidative stress and neuronal death [21]. Intracellular Aβ can modulate the autophagy process by RAGEcalcium-CaMKKβ-AMPK pathway [26] or by generating ROS by mitochondrial damage [27]
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