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Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain

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Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain

dc.contributor.author	Marinelli, Rita
dc.contributor.author	Torquato, Pierangelo
dc.contributor.author	Bartolini, Desirée
dc.contributor.author	Mas Bargues, Cristina
dc.contributor.author	Bellezza, Guido
dc.contributor.author	Gioiello, Antimo
dc.contributor.author	Borras Blasco, Consuelo
dc.contributor.author	De Luca, Antonella
dc.contributor.author	Fallarino, Francesca
dc.contributor.author	Sebastiani, Bartolomeo
dc.contributor.author	Mani, Sridhar
dc.contributor.author	Sidoni, Angelo
dc.contributor.author	Viña Ribes, José
dc.contributor.author	Leri, Manuela
dc.contributor.author	Bucciantini, Monica
dc.contributor.author	Nardiello, Pamela
dc.contributor.author	Casamenti, Fiorella
dc.contributor.author	Galli, Francesco
dc.date.accessioned	2020-11-23T09:40:15Z
dc.date.available	2020-11-23T09:40:15Z
dc.date.issued	2020
dc.identifier.citation	Marinelli, Rita Torquato, Pierangelo Bartolini, Desirée Mas Bargues, Cristina Bellezza, Guido Gioiello, Antimo Borras Blasco, Consuelo De Luca, Antonella Fallarino, Francesca Sebastiani, Bartolomeo Mani, Sridhar Sidoni, Angelo Viña Ribes, José Leri, Manuela Bucciantini, Monica Nardiello, Pamela Casamenti, Fiorella Galli, Francesco 2020 Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain Journal of biological chemistry (Online) Aug 14 295 (33) 11866 11876
dc.identifier.uri	https://hdl.handle.net/10550/76434
dc.description.abstract	Garcinoic acid (GA or δ-T3-13'COOH), is a natural vitamin E metabolite that has preliminarily been identified as a modulator of nuclear receptors involved in β-amyloid (Aβ) metabolism and progression of Alzheimer's disease (AD). In this study, we investigated GA's effects on Aβ oligomer formation and deposition. Specifically, we compared them with those of other vitamin E analogs and the soy isoflavone genistein, a natural agonist of peroxisome proliferator-activated receptor γ (PPARγ) that has therapeutic potential for managing AD. GA significantly reduced Aβ aggregation and accumulation in mouse cortical astrocytes. Similarly to genistein, GA up-regulated PPARγ expression and apolipoprotein E (ApoE) efflux in these cells with an efficacy that was comparable with that of its metabolic precursor δ-tocotrienol and higher than those of α-tocopherol metabolites. Unlike for genistein and the other vitamin E compounds, the GA-induced restoration of ApoE efflux was not affected by pharmacological inhibition of PPARγ activity, and specific activation of pregnane X receptor (PXR) was observed together with ApoE and multidrug resistance protein 1 (MDR1) membrane transporter up-regulation in both the mouse astrocytes and brain tissue. These effects of GA were associated with reduced Aβ deposition in the brain of TgCRND8 mice, a transgenic AD model. In conclusion, GA holds potential for preventing Aβ oligomerization and deposition in the brain. The mechanistic aspects of GA's properties appear to be distinct from those of other vitamin E metabolites and of genistein.
dc.language.iso	eng
dc.relation.ispartof	Journal of biological chemistry (Online), 2020, vol. Aug 14, num. 295 (33), p. 11866-11876
dc.subject	Fisiologia
dc.subject	Biologia
dc.title	Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain
dc.type	journal article	es_ES
dc.date.updated	2020-11-23T09:40:15Z
dc.identifier.doi	10.1074/jbc.RA120.013303
dc.identifier.idgrec	141369
dc.rights.accessRights	open access	es_ES