title: Clearing Amyloid-β through PPARγ/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer's Disease.
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.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia/INCLIVA, Valencia, Spain.
authors.forename: Vicent
authors.initials: V
authors.lastname: Bonet-Costa
authors.affiliation: 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.
authors.forename: Vicente
authors.initials: V
authors.lastname: Herranz-Pérez
authors.affiliation: Department of Psychobiology, Faculty of Psychology, University of Valencia, Valencia, Spain.
authors.forename: MariCarmen
authors.initials: M
authors.lastname: Blanco-Gandía
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia/INCLIVA, Valencia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mas-Bargues
authors.affiliation: Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, Valencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Inglés
authors.affiliation: Laboratory of Comparative Neurobiology, Institute Cavanilles, University of Valencia, CIBERNED, Valencia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Garcia-Tarraga
authors.affiliation: Department of Psychobiology, Faculty of Psychology, University of Valencia, Valencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Rodriguez-Arias
authors.affiliation: Department of Psychobiology, Faculty of Psychology, University of Valencia, Valencia, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Miñarro
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia/INCLIVA, Valencia, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Borras
authors.affiliation: 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.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Garcia-Verdugo
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia/INCLIVA, Valencia, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Viña
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001362:Avoidance Learning / Q000187:drug effects; D000077610:Bexarotene; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D018782:Maze Learning; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D055696:Olfactory Perception / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D021641:Recognition, Psychology / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D047495:PPAR gamma; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene; D019833:Genistein
keywords: Aging; biomedical research; neurodegenerative disease; neuroscience; phytoestrogens