scienze della vita roma, 22-23 ottobre 2012 - SIF

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UNRAVELING THE BENEFICIAL EFFECTS OF OLEUROPEIN AGLYCONE AGAINST ALZHEIMER'S DISEASE Massimo Stefani e Stefania Rigacci Department of Biochemical Sciences, University of Florence The presence, in several brain areas, of plaque deposits whose main component is a fibrillar mesh of the β-amyloid(1-42) (Aβ42) peptide results in functional and cognitive alterations characterizing Alzheimer’s disease (AD). Plaque load results from complex equilibria between Aβ deposition and clearance, where autophagy, a lysosome-mediated catabolic pathway responsible for turnover of long-lived proteins and organelles, notably mitochondria, appears to perform a key role. Autophagy protects neurons against Aβ-induced cytotoxicity suggesting its possible role in Aβ clearance; moreover, autophagy is protective, among others, against ageing, neurodegeneration and cancer, and the induction of autophagy by reduced caloric intake or by rapamycin in mouse models of AD results in decreased intraneuronal accumulation of Aβ, decreased brain levels of pathogenic Aβ42 and a reduced age-dependent accumulation of phosphorylated and aggregated tau. Presently, the early pre-fibrillar assemblies of the Aβ peptides appearing at the onset of fibril growth are considered the main players of amyloid toxicity to neurons; accordingly, one of the directions of the research in AD therapy is developing molecules able to avoid the appearance of toxic oligomeric intermediates. Focusing dietary regimens associated with a reduced risk of AD in the aged population can be useful to find out molecules exploitable for AD therapy. Mounting evidence supports the beneficial effects of the Mediterranean diet (MD) in preventing age-related dysfunctions, cancer and cardiovascular events; MD also reduces the risk and incidence of stroke, cerebrovascular and neurodegenerative diseases and attenuates AD-like pathology and cognitive deterioration. In particular, MD appears to be effective against mild cognitive impairment, which commonly precedes the appearance of severe AD symptoms, and its conversion to AD. Studies in rodents suggest that diet supplementation with polyphenols present in major components of the MD such as red wine and extra virgin olive oil (EVOO) improves learning and behavioural deficits associated with aging and disease. Several reports, including the “Three city study” support a strict association between many protective effects of the MD and the sustained assumption of extra virgin olive oil (EVOO). In particular, a number of polyphenols and secoiridoids found in EVOO, including oleocanthal, hydroxythyrosol and oleuropein aglycone (OLE) have been considered potentially responsible for the beneficial effect of MD, also taking into account their demonstrated ability to cross the blood-brain barrier. Here it is reported that oleuropein aglycone (OLE), the main polyphenol found in EVOO protects the TgCRND8 mouse model of Alzheimer’s disease reducing significantly transgene-associated behavioral impairment. Tg mice fed for two months with a 5% fat diet supplemented with OLE (50 mg/kg of diet) displayed increased body weight and a better general condition without behavioral alterations including hyperactivity. More importantly, they got significantly better scores in learning and memory tests such as the step-down avoidance and the object recognition tests with respect to their littermates fed without OLE, reaching the same level of w.t. mice. Optimal protection was found when OLE supplementation was started at one month of age, when mice brain parenchyma still lacks evident plaque deposition in this animal model, whereas it was increasingly reduced with the delay of the onset of treatment. Data obtained with cultured cells and immunohistochemical analysis of cortical tissue in OLE-fed mice showed a remarkable reduction of both size and compactness of plaques, which appeared “fluffy”. Finally, OLE-fed mice brain displayed reduced astrocite reaction, oxidative stress and apoptosis. However, the most striking effect of OLE supplementation both in Tg and in w.y. mice, as well as in cultured cells, was a strong increase of 18
the expression of autophagy markers, possibly resulting from mTOR inhibition, together with a remarkable enhancement of the lysosomal pathway of protein degradation. Overall, our behavioral, histochemical and biochemical data support the importance of OLE, or one of its derivatives arising from tissue metabolism, as a key player of the reported beneficial effects of the Mediterranean diet against neurodegeneration and AD. 19
Page 1 and 2: CONSORZIO INTERUNIVERSITARIO X CONV
Page 3: INDICE Programma X Convegno Naziona
Page 6 and 7: PROF.SSA ADRIANA MAGGI - Univ. MI
Page 9 and 10: RELAZIONE INTRODUTTIVA E’ la prim
Page 11 and 12: quinto e sesto posto ed hanno un nu
Page 13: ABSTRACT DELLE COMUNICAZIONI SCIENT
Page 16 and 17: REDOX REGULATION OF CELLULAR STRESS
Page 21 and 22: Sessione “Nanobiotecnologie” 21
Page 23 and 24: compositi a partire da una moltepli
Page 25 and 26: SCAFFOLDS BIOCOMPATIBILI PER LA RIG
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Page 29 and 30: NANOMATERIALI: APPLICAZIONI NELL’
Page 31 and 32: Sessione “Interferenti Endocrini
Page 33 and 34: IL PROBLEMA DEGLI EDS:L'ORATA E LA
Page 35 and 36: EFFETTI DEI DISTRUTTORI ENDOCRINI S
Page 37 and 38: APPROCCI TRADIZIONALI E MODERNI PER
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Page 41 and 42: Marco Biglietto AB SCIEX Italy PUSH
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Page 51 and 52: NUTRACEUTICI: DA COADIUVANTI A FARM
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UNITÀ DI RICERCA DEL CONSORZIO INT
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Francesco Giansanti, Loris Leboffe
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5 Federico M., Bagella L. Histone d
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5. Bettati, S., Pasqualetto, E., Lo
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RESPONSABILE SCIENTIFICO CUTRUZZOL
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RESPONSABILE SCIENTIFICO BETTUZZI S
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Prof. Alan Crozier Plant Products a
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8. Canesi L, Negri A, Barmo C, Bann
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3. GIOACCHINI, G, GIORGINI, E,. MER
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3. Winkelmann J, Calloni G, Campion
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Microglia and neuroprotection: from
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6) A. TONELLI, T. TEDESCHI, A. GERM
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PUBBLICAZIONI PIÙ SIGNIFICATIVE NE
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Linea di ricerca 2 - messa a punto
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11. E. Saino, M.L. Focarete, C. Gua
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disfunzione endoteliale, l'omociste
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SEZIONE INBB DI APPARTENENZA Catani
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Workstation L’unita’ di ricerca
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L’importanza di tale considerazio
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RESPONSABILE SCIENTIFICO RODA ALDO
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PRINCIPALI ATTREZZATURE DI CUI DISP
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scienze della vita roma, 22-23 ottobre 2012 - SIF

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