Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 5010741, 12 pages
https://doi.org/10.1155/2018/5010741
Review Article

Benefit of Oleuropein Aglycone for Alzheimer’s Disease by Promoting Autophagy

1Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, UAM, Arzobispo Morcillo 4, 28029 Madrid, Spain
2Molecular Oncology Unit, CIEMAT, Complutense 40, 28040 Madrid, Spain
3Biomedical Research Institute I+12, University Hospital 12 de Octubre, Avenida de Córdoba s/n, 28041 Madrid, Spain
4Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
5Centro de Biología Molecular “Severo Ochoa” (UAM-CSIC), Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain
6Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Valderrebollo 5, 28031 Madrid, Spain
7Neuro-oncology Unit, Instituto de Salud Carlos III-UFIEC, Crtra, Pozuelo Km 2, Majadahonda, 28220 Madrid, Spain

Correspondence should be addressed to Ricardo Gargini; se.cisc.mbc@inigragar and Vega García-Escudero; se.mau@oreducse-aicrag.v

Received 3 December 2017; Accepted 21 January 2018; Published 20 February 2018

Academic Editor: David Vauzour

Copyright © 2018 Joaquín G. Cordero et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. Blennow and H. Hampel, “CSF markers for incipient Alzheimer’s disease,” The Lancet Neurology, vol. 2, no. 10, pp. 605–613, 2003. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Wimo, L. Jönsson, J. Bond, M. Prince, B. Winblad, and Alzheimer Disease International, “The worldwide economic impact of dementia 2010,” Alzheimers Dement, vol. 9, no. 1, pp. 1–11.e3, 2013. View at Publisher · View at Google Scholar · View at Scopus
  3. N. D. Barnard, A. I. Bush, A. Ceccarelli et al., “Dietary and lifestyle guidelines for the prevention of Alzheimer’s disease,” Neurobiology of Aging, vol. 35, Supplement 2, pp. S74–S78, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. M. G. Spillantini and M. Goedert, “Tau pathology and neurodegeneration,” The Lancet Neurology, vol. 12, no. 6, pp. 609–622, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. Y. W. Zhang, R. Thompson, H. Zhang, and H. Xu, “APP processing in Alzheimer’s disease,” Molecular Brain, vol. 4, no. 1, p. 3, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. R. J. Castellani, R. K. Rolston, and M. A. Smith, “Alzheimer disease,” Disease-a-Month, vol. 56, no. 9, pp. 484–546, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Rostagno, J. L. Holton, T. Lashley, T. Revesz, and J. Ghiso, “Cerebral amyloidosis: amyloid subunits, mutants and phenotypes,” Cellular and Molecular Life Sciences, vol. 67, no. 4, pp. 581–600, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. Y. K. Chuah, R. Basir, H. Talib, T. H. Tie, and N. Nordin, “Receptor for advanced glycation end products and its involvement in inflammatory diseases,” International Journal of Inflammation, vol. 2013, Article ID 403460, 15 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. V. I. Korolchuk, F. M. Menzies, and D. C. Rubinsztein, “Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome systems,” FEBS Letters, vol. 584, no. 7, pp. 1393–1398, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. D. J. Klionsky, “Autophagy: from phenomenology to molecular understanding in less than a decade,” Nature Reviews Molecular Cell Biology, vol. 8, no. 11, pp. 931–937, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. F. M. Menzies, A. Fleming, and D. C. Rubinsztein, “Compromised autophagy and neurodegenerative diseases,” Nature Reviews Neuroscience, vol. 16, no. 6, pp. 345–357, 2015. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Alers, A. S. Loffler, S. Wesselborg, and B. Stork, “Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks,” Molecular and Cellular Biology, vol. 32, no. 1, pp. 2–11, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. R. A. Nixon, “The role of autophagy in neurodegenerative disease,” Nature Medicine, vol. 19, no. 8, pp. 983–997, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. Y. Kabeya, N. Mizushima, T. Ueno et al., “LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing,” The EMBO Journal, vol. 19, no. 21, pp. 5720–5728, 2000. View at Publisher · View at Google Scholar
  15. T. Johansen and T. Lamark, “Selective autophagy mediated by autophagic adapter proteins,” Autophagy, vol. 7, no. 3, pp. 279–296, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. T. H. Clausen, T. Lamark, P. Isakson et al., “p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy,” Autophagy, vol. 6, no. 3, pp. 330–344, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. I. Novak, V. Kirkin, D. G. McEwan et al., “Nix is a selective autophagy receptor for mitochondrial clearance,” EMBO Reports, vol. 11, no. 1, pp. 45–51, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. D. J. Klionsky, K. Abdelmohsen, A. Abe et al., “Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition),” Autophagy, vol. 12, no. 1, pp. 1–222, 2016. View at Publisher · View at Google Scholar · View at Scopus
  19. Z. Yang and D. J. Klionsky, “Permeases recycle amino acids resulting from autophagy,” Autophagy, vol. 3, no. 2, pp. 149-150, 2007. View at Publisher · View at Google Scholar
  20. H. Pi, M. Li, L. Tian, Z. Yang, Z. Yu, and Z. Zhou, “Enhancing lysosomal biogenesis and autophagic flux by activating the transcription factor EB protects against cadmium-induced neurotoxicity,” Scientific Reports, vol. 7, article 43466, 2017. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Zare-Shahabadi, E. Masliah, G. V. Johnson, and N. Rezaei, “Autophagy in Alzheimer’s disease,” Reviews in the Neurosciences, vol. 26, no. 4, pp. 385–395, 2015. View at Publisher · View at Google Scholar · View at Scopus
  22. F. Pickford, E. Masliah, M. Britschgi et al., “The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice,” The Journal of Clinical Investigation, vol. 118, no. 6, pp. 2190–2199, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. P. Martín-Maestro, R. Gargini, G. Perry, J. Avila, and V. García-Escudero, “PARK2 enhancement is able to compensate mitophagy alterations found in sporadic Alzheimer’s disease,” Human Molecular Genetics, vol. 25, no. 4, pp. 792–806, 2016. View at Publisher · View at Google Scholar · View at Scopus
  24. J. Lu, L. He, C. Behrends et al., “NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity,” Nature Communications, vol. 5, p. 3920, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. C. Yang, C. Z. Cai, J. X. Song et al., “NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models,” Autophagy, vol. 13, no. 12, pp. 2028–2040, 2017. View at Publisher · View at Google Scholar
  26. S. M. Son, E. S. Jung, H. J. Shin, J. Byun, and I. Mook-Jung, “Aβ-induced formation of autophagosomes is mediated by RAGE-CaMKKβ-AMPK signaling,” Neurobiology Aging, vol. 33, no. 5, pp. 1006.e11–1006.e23, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. V. Garcia-Escudero et al., “Deconstructing mitochondrial dysfunction in Alzheimer disease,” Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 162152, 13 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  28. J. Cooper-Knock, J. Kirby, L. Ferraiuolo, P. R. Heath, M. Rattray, and P. J. Shaw, “Gene expression profiling in human neurodegenerative disease,” Nature Reviews Neurology, vol. 8, no. 9, pp. 518–530, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. R. X. Santos, S. C. Correia, X. Wang et al., “A synergistic dysfunction of mitochondrial fission/fusion dynamics and mitophagy in Alzheimer’s disease,” Journal of Alzheimer's Disease, vol. 20, Supplement 2, pp. S401–S412, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. N. C. Berchtold, D. H. Cribbs, P. D. Coleman et al., “Gene expression changes in the course of normal brain aging are sexually dimorphic,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 40, pp. 15605–15610, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Caccamo, S. Majumder, A. Richardson, R. Strong, and S. Oddo, “Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-β, and Tau: effects on cognitive impairments,” The Journal of Biological Chemistry, vol. 285, no. 17, pp. 13107–13120, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. X. Zhang, L. Li, S. Chen et al., “Rapamycin treatment augments motor neuron degeneration in SOD1G93A mouse model of amyotrophic lateral sclerosis,” Autophagy, vol. 7, no. 4, pp. 412–425, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. P. J. Khandelwal, A. M. Herman, H. S. Hoe, G. W. Rebeck, and C. E. H. Moussa, “Parkin mediates beclin-dependent autophagic clearance of defective mitochondria and ubiquitinated Aβ in AD models,” Human Molecular Genetics, vol. 20, no. 11, pp. 2091–2102, 2011. View at Publisher · View at Google Scholar · View at Scopus
  34. I. Lonskaya, A. R. Shekoyan, M. L. Hebron, N. Desforges, N. K. Algarzae, and C. E. Moussa, “Diminished parkin solubility and co-localization with intraneuronal amyloid-β are associated with autophagic defects in Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 33, no. 1, pp. 231–247, 2013. View at Publisher · View at Google Scholar · View at Scopus
  35. D. S. Yang, P. Stavrides, P. S. Mohan et al., “Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer’s disease ameliorates amyloid pathologies and memory deficits,” Brain, vol. 134, no. 1, pp. 258–277, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. S. Majumder, A. Richardson, R. Strong, and S. Oddo, “Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits,” PLoS One, vol. 6, no. 9, article e25416, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. H. Soininen, A. Solomon, P. J. Visser et al., “24-month intervention with a specific multinutrient in people with prodromal Alzheimer’s disease (LipiDiDiet): a randomised, double-blind, controlled trial,” The Lancet Neurology, vol. 16, no. 12, pp. 965–975, 2017. View at Publisher · View at Google Scholar
  38. C. Dussaillant, G. Echeverría, I. Urquiaga, N. Velasco, and A. Rigotti, “Evidencia actual sobre los beneficios de la dieta mediterránea en salud,” Revista Médica de Chile, vol. 144, no. 8, pp. 1990–1997, 2016. View at Publisher · View at Google Scholar
  39. C. Feart, C. Samieri, and P. Barberger-Gateau, “Mediterranean diet and cognitive function in older adults,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 13, no. 1, pp. 14–18, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. N. Scarmeas, Y. Stern, M. X. Tang, R. Mayeux, and J. A. Luchsinger, “Mediterranean diet and risk for Alzheimer’s disease,” Annals of Neurology, vol. 59, no. 6, pp. 912–921, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. C. Féart, C. Samieri, V. Rondeau et al., “Adherence to a Mediterranean diet, cognitive decline, and risk of dementia,” JAMA, vol. 302, no. 6, pp. 638–648, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. C. Berr, F. Portet, I. Carriere et al., “Olive oil and cognition: results from the three-city study,” Dementia and Geriatric Cognitive Disorders, vol. 28, no. 4, pp. 357–364, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. A. H. Abuznait, H. Qosa, B. A. Busnena, K. A. el Sayed, and A. Kaddoumi, “Olive-oil-derived oleocanthal enhances β-amyloid clearance as a potential neuroprotective mechanism against Alzheimer’s disease: in vitro and in vivo studies,” ACS Chemical Neuroscience, vol. 4, no. 6, pp. 973–982, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. S. A. Farr, T. O. Price, L. J. Dominguez et al., “Extra virgin olive oil improves learning and memory in SAMP8 mice,” Journal of Alzheimer's Disease, vol. 28, no. 1, pp. 81–92, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. H. Qosa, L. A. Mohamed, Y. S. Batarseh et al., “Extra-virgin olive oil attenuates amyloid-β and tau pathologies in the brains of TgSwDI mice,” The Journal of Nutritional Biochemistry, vol. 26, no. 12, pp. 1479–1490, 2015. View at Publisher · View at Google Scholar · View at Scopus
  46. C. Valls-Pedret, R. M. Lamuela-Raventós, A. Medina-Remón et al., “Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk,” Journal of Alzheimer's Disease, vol. 29, no. 4, pp. 773–782, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. V. Pitozzi, M. Jacomelli, M. Zaid et al., “Effects of dietary extra-virgin olive oil on behaviour and brain biochemical parameters in ageing rats,” British Journal of Nutrition, vol. 103, no. 11, pp. 1674–1683, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. K. Pallauf and G. Rimbach, “Autophagy, polyphenols and healthy ageing,” Ageing Research Reviews, vol. 12, no. 1, pp. 237–252, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. R. Tsao, “Chemistry and biochemistry of dietary polyphenols,” Nutrients, vol. 2, no. 12, pp. 1231–1246, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Stefani and S. Rigacci, “Beneficial properties of natural phenols: highlight on protection against pathological conditions associated with amyloid aggregation,” BioFactors, vol. 40, no. 5, pp. 482–493, 2014. View at Publisher · View at Google Scholar · View at Scopus
  51. N. Hasima and B. Ozpolat, “Regulation of autophagy by polyphenolic compounds as a potential therapeutic strategy for cancer,” Cell Death & Disease, vol. 5, no. 11, article e1509, 2014. View at Publisher · View at Google Scholar · View at Scopus
  52. H. Lewandowska, M. Kalinowska, W. Lewandowski, T. M. Stępkowski, and K. Brzóska, “The role of natural polyphenols in cell signaling and cytoprotection against cancer development,” The Journal of Nutritional Biochemistry, vol. 32, pp. 1–19, 2016. View at Publisher · View at Google Scholar · View at Scopus
  53. G. Gossner, M. Choi, L. Tan et al., “Genistein-induced apoptosis and autophagocytosis in ovarian cancer cells,” Gynecologic Oncology, vol. 105, no. 1, pp. 23–30, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. A. B. Kunnumakkara, P. Anand, and B. B. Aggarwal, “Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins,” Cancer Letters, vol. 269, no. 2, pp. 199–225, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. E. Maioli, L. Greci, K. Soucek et al., “Rottlerin inhibits ROS formation and prevents NFκB activation in MCF-7 and HT-29 cells,” Journal of Biomedicine and Biotechnology, vol. 2009, Article ID 742936, 7 pages, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. B. Ozpolat, U. Akar, K. Mehta, and G. Lopez-Berestein, “PKCδ and tissue transglutaminase are novel inhibitors of autophagy in pancreatic cancer cells,” Autophagy, vol. 3, no. 5, pp. 480–483, 2007. View at Publisher · View at Google Scholar
  57. M. Sandri, “FOXOphagy path to inducing stress resistance and cell survival,” Nature Cell Biology, vol. 14, no. 8, pp. 786–788, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. C. Soler-Rivas, J. C. Espín, and H. J. Wichers, “Oleuropein and related compounds,” Journal of the Science of Food and Agriculture, vol. 80, no. 7, pp. 1013–1023, 2000. View at Publisher · View at Google Scholar
  59. F. Gutierrez-Rosales, M. P. Romero, M. Casanovas, M. J. Motilva, and M. I. Mínguez-Mosquera, “Metabolites involved in oleuropein accumulation and degradation in fruits of Olea europaea L.: Hojiblanca and Arbequina varieties,” Journal of Agricultural and Food Chemistry, vol. 58, no. 24, pp. 12924–12933, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. R. Mateos, A. Cert, M. C. Pérez-Camino, and J. M. García, “Evaluation of virgin olive oil bitterness by quantification of secoiridoid derivatives,” Journal of the American Oil Chemists' Society, vol. 81, no. 1, pp. 71–75, 2004. View at Publisher · View at Google Scholar
  61. M. Esti, L. Cinquanta, and E. La Notte, “Phenolic compounds in different olive varieties,” Journal of Agricultural and Food Chemistry, vol. 46, no. 1, pp. 32–35, 1998. View at Publisher · View at Google Scholar
  62. M. P. Carrera-González, M. J. Ramírez-Expósito, M. D. Mayas, and J. M. Martínez-Martos, “Protective role of oleuropein and its metabolite hydroxytyrosol on cancer,” Trends in Food Science & Technology, vol. 31, no. 2, pp. 92–99, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. E. Fuentes and I. Palomo, “Antiplatelet effects of natural bioactive compounds by multiple targets: food and drug interactions,” Journal of Functional Foods, vol. 6, Supplement C, no. 6, pp. 73–81, 2014. View at Publisher · View at Google Scholar · View at Scopus
  64. L. Rubió, A. Serra, A. Macià, C. Piñol, M. P. Romero, and M. J. Motilva, “In vivo distribution and deconjugation of hydroxytyrosol phase II metabolites in red blood cells: a potential new target for hydroxytyrosol,” Journal of Functional Foods, vol. 10, Supplement C, pp. 139–143, 2014. View at Publisher · View at Google Scholar · View at Scopus
  65. M. V. Sepporta, R. Fuccelli, P. Rosignoli et al., “Oleuropein inhibits tumour growth and metastases dissemination in ovariectomised nude mice with MCF-7 human breast tumour xenografts,” Journal of Functional Foods, vol. 8, Supplement C, pp. 269–273, 2014. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Daccache, C. Lion, N. Sibille et al., “Oleuropein and derivatives from olives as Tau aggregation inhibitors,” Neurochemistry International, vol. 58, no. 6, pp. 700–707, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. L. Diomede, S. Rigacci, M. Romeo, M. Stefani, and M. Salmona, “Oleuropein aglycone protects transgenic C. elegans strains expressing Aβ42 by reducing plaque load and motor deficit,” PLoS One, vol. 8, no. 3, article e58893, 2013. View at Publisher · View at Google Scholar · View at Scopus
  68. I. Luccarini, C. Grossi, S. Rigacci et al., “Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates,” Neurobiology of Aging, vol. 36, no. 2, pp. 648–663, 2015. View at Publisher · View at Google Scholar · View at Scopus
  69. F. Casamenti, C. Grossi, S. Rigacci, D. Pantano, I. Luccarini, and M. Stefani, “Oleuropein aglycone: a possible drug against degenerative conditions. In vivo evidence of its effectiveness against Alzheimer’s disease,” Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 679–688, 2015. View at Publisher · View at Google Scholar · View at Scopus
  70. C. Grossi, S. Rigacci, S. Ambrosini et al., “The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology,” PLoS One, vol. 8, no. 8, article e71702, 2013. View at Publisher · View at Google Scholar · View at Scopus
  71. S. Rigacci, C. Miceli, C. Nediani et al., “Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: a mechanistic insight,” Oncotarget, vol. 6, no. 34, pp. 35344–35357, 2015. View at Publisher · View at Google Scholar · View at Scopus
  72. V. Vingtdeux, L. Giliberto, H. Zhao et al., “AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-β peptide metabolism,” The Journal of Biological Chemistry, vol. 285, no. 12, pp. 9100–9113, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. J. Zhou, B. L. Farah, R. A. Sinha et al., “Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, stimulates hepatic autophagy and lipid clearance,” PLoS One, vol. 9, no. 1, article e87161, 2014. View at Publisher · View at Google Scholar · View at Scopus
  74. R. T. Marquez and L. Xu, “Bcl-2:Beclin 1 complex: multiple, mechanisms regulating autophagy/apoptosis toggle switch,” American Journal of Cancer Research, vol. 2, no. 2, pp. 214–221, 2012. View at Google Scholar
  75. R. C. Russell, Y. Tian, H. Yuan et al., “ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase,” Nature Cell Biology, vol. 15, no. 7, pp. 741–750, 2013. View at Publisher · View at Google Scholar · View at Scopus
  76. F. Ng and B. L. Tang, “Sirtuins’ modulation of autophagy,” Journal of Cellular Physiology, vol. 228, no. 12, pp. 2262–2270, 2013. View at Publisher · View at Google Scholar · View at Scopus
  77. I. Luccarini, D. Pantano, P. Nardiello et al., “The polyphenol oleuropein aglycone modulates the PARP1-SIRT1 interplay: an in vitro and in vivo study,” Journal of Alzheimer's Disease, vol. 54, no. 2, pp. 737–750, 2016. View at Publisher · View at Google Scholar · View at Scopus
  78. S. Chung, H. Yao, S. Caito, J.w. Hwang, G. Arunachalam, and I. Rahman, “Regulation of SIRT1 in cellular functions: role of polyphenols,” Archives of Biochemistry and Biophysics, vol. 501, no. 1, pp. 79–90, 2010. View at Publisher · View at Google Scholar · View at Scopus
  79. L. Adwan and N. H. Zawia, “Epigenetics: a novel therapeutic approach for the treatment of Alzheimer’s disease,” Pharmacology & Therapeutics, vol. 139, no. 1, pp. 41–50, 2013. View at Publisher · View at Google Scholar · View at Scopus
  80. S. M. Henning, P. Wang, C. L. Carpenter, and D. Heber, “Epigenetic effects of green tea polyphenols in cancer,” Epigenomics, vol. 5, no. 6, pp. 729–741, 2013. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Sardiello, M. Palmieri, A. di Ronza et al., “A gene network regulating lysosomal biogenesis and function,” Science, vol. 325, no. 5939, pp. 473–477, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. C. Settembre, C. di Malta, V. A. Polito et al., “TFEB links autophagy to lysosomal biogenesis,” Science, vol. 332, no. 6036, pp. 1429–1433, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. C. Settembre, R. Zoncu, D. L. Medina et al., “A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB,” The EMBO Journal, vol. 31, no. 5, pp. 1095–1108, 2012. View at Publisher · View at Google Scholar · View at Scopus
  84. D. L. Medina, S. di Paola, I. Peluso et al., “Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB,” Nature Cell Biology, vol. 17, no. 3, pp. 288–299, 2015. View at Publisher · View at Google Scholar · View at Scopus
  85. M. N. Vissers, P. L. Zock, A. J. C. Roodenburg, R. Leenen, and M. B. Katan, “Olive oil phenols are absorbed in humans,” The Journal of Nutrition, vol. 132, no. 3, pp. 409–417, 2002. View at Publisher · View at Google Scholar
  86. M. de Bock, E. B. Thorstensen, J. G. B. Derraik, H. V. Henderson, P. L. Hofman, and W. S. Cutfield, “Human absorption and metabolism of oleuropein and hydroxytyrosol ingested as olive (Olea europaea L.) leaf extract,” Molecular Nutrition & Food Research, vol. 57, no. 11, pp. 2079–2085, 2013. View at Publisher · View at Google Scholar · View at Scopus
  87. S. H. Omar, “Oleuropein in olive and its pharmacological effects,” Scientia Pharmaceutica, vol. 78, no. 2, pp. 133–154, 2010. View at Publisher · View at Google Scholar · View at Scopus
  88. S. Cetrullo, S. D'Adamo, S. Guidotti, R. M. Borzì, and F. Flamigni, “Hydroxytyrosol prevents chondrocyte death under oxidative stress by inducing autophagy through sirtuin 1-dependent and -independent mechanisms,” Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 1860, no. 6, pp. 1181–1191, 2016. View at Publisher · View at Google Scholar · View at Scopus
  89. D. Pantano, I. Luccarini, P. Nardiello, M. Servili, M. Stefani, and F. Casamenti, “Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology,” British Journal of Clinical Pharmacology, vol. 83, no. 1, pp. 54–62, 2017. View at Publisher · View at Google Scholar · View at Scopus
  90. M. J. Oliveras-López, M. Innocenti, C. Giaccherini, F. Ieri, A. Romani, and N. Mulinacci, “Study of the phenolic composition of spanish and italian monocultivar extra virgin olive oils: distribution of lignans, secoiridoidic, simple phenols and flavonoids,” Talanta, vol. 73, no. 4, pp. 726–732, 2007. View at Publisher · View at Google Scholar · View at Scopus
  91. S. Cicerale, L. J. Lucas, and R. S. J. Keast, “Antimicrobial, antioxidant and anti-inflammatory phenolic activities in extra virgin olive oil,” Current Opinion in Biotechnology, vol. 23, no. 2, pp. 129–135, 2012. View at Publisher · View at Google Scholar · View at Scopus
  92. D. Del Rio, A. Rodriguez-Mateos, J. P. Spencer, M. Tognolini, G. Borges, and A. Crozier, “Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases,” Antioxidants & Redox Signaling, vol. 18, no. 14, pp. 1818–1892, 2013. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Rigacci and M. Stefani, “Nutraceuticals and amyloid neurodegenerative diseases: a focus on natural phenols,” Expert Review of Neurotherapeutics, vol. 15, no. 1, pp. 41–52, 2015. View at Publisher · View at Google Scholar · View at Scopus
  94. F. Márquez-Sandoval, M. Bulló, B. Vizmanos, P. Casas-Agustench, and J. Salas-Salvadó, “Un patrón de alimentación saludable: la dieta mediterránea tradicional,” Antropo, vol. 16, pp. 11–22, 2008. View at Google Scholar