title: Toxicity of Alzheimer's disease-associated Aβ peptide is ameliorated in a Drosophila model by tight control of zinc and copper availability.
abstract: Amyloid plaques consisting of aggregated Aβ peptide are a hallmark of Alzheimer's disease. Among the different forms of Aβ, the one of 42aa length (Aβ42) is most aggregation-prone and also the most neurotoxic. We find that eye-specific expression of human Aβ42 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 Aβ42 expression.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Hua
authors.forename: Lisa
authors.initials: L
authors.lastname: Münter
authors.forename: Anja
authors.initials: A
authors.lastname: Harmeier
authors.forename: Oleg
authors.initials: O
authors.lastname: Georgiev
authors.forename: Gerd
authors.initials: G
authors.lastname: Multhaup
authors.forename: Walter
authors.initials: W
authors.lastname: Schaffner
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila; D005123:Eye / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D019076:Transgenes; D015854:Up-Regulation; D015032:Zinc / Q000378:metabolism*; D000097809:Transcription Factor MTF-1
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D003300:Copper; D004268:DNA-Binding Proteins; D008668:Metallothionein; D010446:Peptide Fragments; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1; C075222:amyloid beta-protein (1-42)