Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast
2011 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 334, no 6060, 1241-1245 p.Article in journal (Refereed) Published
Aβ (beta amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained using yeast as a model system.
Place, publisher, year, edition, pages
Washington: American association of advancement in science , 2011. Vol. 334, no 6060, 1241-1245 p.
genome-wide association, alpha-synuclein, saccharomyces cerevisiae, endoplasmic reticulum, identifies variants, common variants, peptide, oligomers, membrane, cells
Other Basic Medicine
IdentifiersURN: urn:nbn:se:umu:diva-50077DOI: 10.1126/science.1213210ISI: 000297553600041PubMedID: 22033521OAI: oai:DiVA.org:umu-50077DiVA: diva2:458958