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Clearing Amyloid-β through PPARγ/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer's Disease.
J Alzheimers Dis. 2016; 51(3):701-11.JA

Abstract

Amyloid-β (Aβ) clearance from brain, which is decreased in Alzheimer's disease, is facilitated by apolipoprotein E (ApoE). ApoE is upregulated by activation of the retinoid X receptor moiety of the RXR/PPARγ dimeric receptor. Genistein, a non-toxic, well-tested, and inexpensive drug activates the other moiety of the receptor PPARγ. Treatment of an Alzheimer's disease mouse model with genistein results in a remarkable and rapid improvement in various parameters of cognition, such as hippocampal learning, recognition memory, implicit memory, and odor discrimination. This is associated with a lowering of Aβ levels in brain, in the number and the area of amyloid plaques (confirmed in vivo by positron emission tomography) as well as in microglial reactivity. Finally, incubation of primary astrocytes with genistein results in a PPARγ-mediated increased release of ApoE. Our results strongly suggest that controlled clinical trials should be performed to test the effect of genistein as treatment of human Alzheimer's disease.

Authors+Show Affiliations

Department of Physiology, Faculty of Medicine, University of Valencia/INCLIVA, Valencia, Spain.Laboratory of Comparative Neurobiology, Institute Cavanilles, University of Valencia, CIBERNED, Valencia, Spain. Multiple sclerosis and Neuro-regeneration mixed unit, IIS Hospital La Fe, Valencia, Spain.Department of Psychobiology, Faculty of Psychology, University of Valencia, Valencia, Spain.Department of Physiology, Faculty of Medicine, University of Valencia/INCLIVA, Valencia, Spain.Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, Valencia, Spain.Laboratory of Comparative Neurobiology, Institute Cavanilles, University of Valencia, CIBERNED, Valencia, Spain.Department of Psychobiology, Faculty of Psychology, University of Valencia, Valencia, Spain.Department of Psychobiology, Faculty of Psychology, University of Valencia, Valencia, Spain.Department of Physiology, Faculty of Medicine, University of Valencia/INCLIVA, Valencia, Spain.Laboratory of Comparative Neurobiology, Institute Cavanilles, University of Valencia, CIBERNED, Valencia, Spain. Multiple sclerosis and Neuro-regeneration mixed unit, IIS Hospital La Fe, Valencia, Spain.Department of Physiology, Faculty of Medicine, University of Valencia/INCLIVA, Valencia, Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26890773

Citation

Bonet-Costa, Vicent, et al. "Clearing Amyloid-β Through PPARγ/ApoE Activation By Genistein Is a Treatment of Experimental Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 51, no. 3, 2016, pp. 701-11.
Bonet-Costa V, Herranz-Pérez V, Blanco-Gandía M, et al. Clearing Amyloid-β through PPARγ/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer's Disease. J Alzheimers Dis. 2016;51(3):701-11.
Bonet-Costa, V., Herranz-Pérez, V., Blanco-Gandía, M., Mas-Bargues, C., Inglés, M., Garcia-Tarraga, P., Rodriguez-Arias, M., Miñarro, J., Borras, C., Garcia-Verdugo, J. M., & Viña, J. (2016). Clearing Amyloid-β through PPARγ/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer's Disease. Journal of Alzheimer's Disease : JAD, 51(3), 701-11. https://doi.org/10.3233/JAD-151020
Bonet-Costa V, et al. Clearing Amyloid-β Through PPARγ/ApoE Activation By Genistein Is a Treatment of Experimental Alzheimer's Disease. J Alzheimers Dis. 2016;51(3):701-11. PubMed PMID: 26890773.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clearing Amyloid-β through PPARγ/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer's Disease. AU - Bonet-Costa,Vicent, AU - Herranz-Pérez,Vicente, AU - Blanco-Gandía,MariCarmen, AU - Mas-Bargues,Cristina, AU - Inglés,Marta, AU - Garcia-Tarraga,Patricia, AU - Rodriguez-Arias,Marta, AU - Miñarro,Jose, AU - Borras,Consuelo, AU - Garcia-Verdugo,Jose Manuel, AU - Viña,Jose, PY - 2016/2/19/entrez PY - 2016/2/19/pubmed PY - 2016/12/20/medline KW - Aging KW - biomedical research KW - neurodegenerative disease KW - neuroscience KW - phytoestrogens SP - 701 EP - 11 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 51 IS - 3 N2 - Amyloid-β (Aβ) clearance from brain, which is decreased in Alzheimer's disease, is facilitated by apolipoprotein E (ApoE). ApoE is upregulated by activation of the retinoid X receptor moiety of the RXR/PPARγ dimeric receptor. Genistein, a non-toxic, well-tested, and inexpensive drug activates the other moiety of the receptor PPARγ. Treatment of an Alzheimer's disease mouse model with genistein results in a remarkable and rapid improvement in various parameters of cognition, such as hippocampal learning, recognition memory, implicit memory, and odor discrimination. This is associated with a lowering of Aβ levels in brain, in the number and the area of amyloid plaques (confirmed in vivo by positron emission tomography) as well as in microglial reactivity. Finally, incubation of primary astrocytes with genistein results in a PPARγ-mediated increased release of ApoE. Our results strongly suggest that controlled clinical trials should be performed to test the effect of genistein as treatment of human Alzheimer's disease. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/26890773/Clearing_Amyloid_β_through_PPARγ/ApoE_Activation_by_Genistein_is_a_Treatment_of_Experimental_Alzheimer's_Disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-151020 DB - PRIME DP - Unbound Medicine ER -