Garcinoic acid prevents beta-amyloid (Abeta) deposition in the mouse brain
| العنوان: | Garcinoic acid prevents beta-amyloid (Abeta) deposition in the mouse brain |
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| المؤلفون: | Marinelli R, Torquato P, Bartolini D, Mas-Bargues C, Bellezza G, Gioiello A, Borras C, De Luca A, Fallarino F, Sebastiani B, Mani S, Sidoni A, Vina J, Leri M, Bucciantini M, Nardiello P, Casamenti F, Galli F |
| المصدر: | JOURNAL OF BIOLOGICAL CHEMISTRY r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA instname |
| بيانات النشر: | American Society for Biochemistry and Molecular Biology Inc., 2020. |
| سنة النشر: | 2020 |
| الوصف: | Garcinoic acid (GA or delta-T3-13'COOH), is a natural vitamin E metabolite that has preliminarily been identified as a modulator of nuclear receptors involved in beta-amyloid (Abeta) metabolism and progression of Alzheimer's disease (AD). In this study, we investigated GA's effects on Abeta 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 gamma (PPARgamma) that has therapeutic potential for managing AD. GA significantly reduced Abeta aggregation and accumulation in mouse cortical astrocytes. Similarly to genistein, GA up-regulated PPARgamma expression and apolipoprotein E (ApoE) efflux in these cells with an efficacy that was comparable to that of its metabolic precursor delta-tocotrienol and higher than those of alpha-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 PPARgamma 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 Abeta deposition in the brain of TgCRND8 mice, a transgenic AD model. In conclusion, GA holds potential for preventing Abeta 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. Published under license by The American Society for Biochemistry and Molecular Biology, Inc. |
| تدمد: | 0021-9258 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=RECOLECTA___::e472aaeafb0a4cdd97958b86629e65e7 https://www.fundanet.incliva.es/publicaciones/ProdCientif/PublicacionFrw.aspx?id=4609 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.RECOLECTA.....e472aaeafb0a4cdd97958b86629e65e7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219258 |
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