Characterization of the role of the antioxidant proteins metallothioneins 1 and 2 in an animal model of Alzheimer's disease

Yasmina Manso, Javier Carrasco, Gemma Comes, Paul A. Adlard, Ashley I. Bush, Juan Hidalgo*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

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. © 2012 Springer Basel AG.
Original languageEnglish
Pages (from-to)3665-3681
JournalCellular and Molecular Life Sciences
Volume69
DOIs
Publication statusPublished - 1 Nov 2012

Keywords

  • Alzheimer' disease
  • Amyloid plaques
  • Behavior
  • Body weight
  • Gliosis
  • Metallothionein
  • Metals
  • Survival
  • Tg2576

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