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Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain.
J Biol Chem. 2020 Jul 02 [Online ahead of print]JB

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 to 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.

Authors+Show Affiliations

University of Perugia, Italy.University of Perugia, Italy.University of Perugia, Italy.University of Valencia, Spain.University of Perugia, Italy.University of Perugia, Italy.University of Valencia, Spain.University of Perugia, Italy.University of Perugia.University of Perugia, Italy.Medicine, Albert Einstein College of Medicine, United States.University of Perugia, Italy.Physiology, University of Valencia, Spain.University of Florence, Italy.Department of Experimental and Clinical Biomedical Sciences, University of Florence, Italy.University of Florence, Italy.University of Florence, Italy.Department of Pharmaceutical Sciences, University of Perugia, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32616652

Citation

Marinelli, Rita, et al. "Garcinoic Acid Prevents Β-amyloid (Aβ) Deposition in the Mouse Brain." The Journal of Biological Chemistry, 2020.
Marinelli R, Torquato P, Bartolini D, et al. Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain. J Biol Chem. 2020.
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. (2020). Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain. The Journal of Biological Chemistry. https://doi.org/10.1074/jbc.RA120.013303
Marinelli R, et al. Garcinoic Acid Prevents Β-amyloid (Aβ) Deposition in the Mouse Brain. J Biol Chem. 2020 Jul 2; PubMed PMID: 32616652.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain. AU - Marinelli,Rita, AU - Torquato,Pierangelo, AU - Bartolini,Desirée, AU - Mas-Bargues,Cristina, AU - Bellezza,Guido, AU - Gioiello,Antimo, AU - Borras,Consuelo, AU - De Luca,Antonella, AU - Fallarino,Francesca, AU - Sebastiani,Bartolomeo, AU - Mani,Sridhar, AU - Sidoni,Angelo, AU - Vina,Jose, AU - Leri,Manuela, AU - Bucciantini,Monica, AU - Nardiello,Pamela, AU - Casamenti,Fiorella, AU - Galli,Francesco, Y1 - 2020/07/02/ PY - 2020/07/02/accepted PY - 2020/03/04/received PY - 2020/7/4/entrez KW - Alzheimer disease KW - Garcinoic Acid KW - amyloid-beta (AB) KW - apolipoprotein E (ApoE) KW - genistein KW - neurodegenerative disease KW - peroxisome proliferator-activated receptor (PPAR) KW - pregnane X receptor (PXR) KW - protein aggregation KW - tocopherol KW - tocotrienol KW - vitamin E JF - The Journal of biological chemistry JO - J. Biol. Chem. N2 - 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 to 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/32616652/Garcinoic_acid_prevents_β-amyloid_(Aβ)_deposition_in_the_mouse_brain L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=32616652 DB - PRIME DP - Unbound Medicine ER -
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