Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 69, Issue 21, Pages 3665-3681Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-012-1045-y
Keywords
Alzheimer' disease; Tg2576; Metallothionein; Behavior; Amyloid plaques; Gliosis; Metals; Survival; Body weight
Categories
Funding
- Ministerio de Ciencia e Innovacion y Cofinanciada por el Fondo Europeo de Desarrollo Regional (FEDER) [SAF2002-01268, SAF2005-00671, SAF2008-00435, SAF2011-23272]
- National Health and Medical Research Council of Australia
- Australian Research Council
- Alzheimer's Association (USA)
- Joan and Peter Clemenger Trust
- [AP2005-0588]
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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.
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