title: Characterization of the role of the antioxidant proteins metallothioneins 1 and 2 in an animal model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is by far the most commonly diagnosed dementia, and despite multiple efforts, there are still no effective drugs available for its treatment. One strategy that deserves to be pursued is to alter the expression and/or physiological action of endogenous proteins instead of administering exogenous factors. In this study, we intend to characterize the roles of the antioxidant, anti-inflammatory, and heavy-metal binding proteins, metallothionein-1 + 2 (MT1 + 2), in a mouse model of Alzheimer's disease, Tg2576 mice. Contrary to expectations, MT1 + 2-deficiency rescued partially the human amyloid precursor protein-induced changes in mortality and body weight in a gender-dependent manner. On the other hand, amyloid plaque burden was decreased in the cortex and hippocampus in both sexes, while the amyloid cascade, neuroinflammation, and behavior were affected in the absence of MT1 + 2 in a complex manner. These results highlight that the control of the endogenous production and/or action of MT1 + 2 could represent a powerful therapeutic target in AD.
authors: Animal Physiology Unit, Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Edificio C, Bellaterra, Barcelona 08193, Spain.
authors: Yasmina
authors: Y
authors: Manso
authors: Javier
authors: J
authors: Carrasco
authors: Gemma
authors: G
authors: Comes
authors: Paul A
authors: PA
authors: Adlard
authors: Ashley I
authors: AI
authors: Bush
authors: Juan
authors: J
authors: Hidalgo
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C491054:Mt2 protein, mouse; D010446:Peptide Fragments; C433241:amyloid beta-protein (1-16); C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D008668:Metallothionein