Toxicity of Alzheimer ’ s disease - associated A peptide is ameliorated in a

Abstract Amyloid plaques consisting of aggregated A� peptide are a hallmark of Alzheimer’s disease. Among the different forms of A�, the one of 42aa length (A�42) is most aggregation-prone and also the most neurotoxic. We find that eye-specific expression of human A�42 in Drosophila results in a degeneration of eye structures that progresses with age. Dietary supplements of zinc or copper ions exacerbate eye damage. Positive effects are seen with zinc/copper chelators, or with elevated expression of MTF-1, a transcription factor with a key role in metal homeostasis and detoxification, or with human or fly transgenes encoding metallothioneins, metal scavenger proteins. These results show that a tight control of zinc and copper availability can minimize cellular damage associated with A�42 expression. DOI: https://doi.org/10.1515/BC.2011.084 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-49283 Accepted Version Originally published at: Hua, H; Münter, L; Harmeier, A; Georgiev, O; Multhaup, G; Schaffner, W (2011). Toxicity of Alzheimer’s disease-associated A� peptide is ameliorated in a Drosophila model by tight control of zinc and copper availability. Biological Chemistry, 392(10):919-926. DOI: https://doi.org/10.1515/BC.2011.084