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Science. 2011 Dec 2;334(6060):1241-5. doi: 10.1126/science.1213210. Epub 2011 Oct 27.

Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast.

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1
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Abstract

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 with yeast as a model system.

PMID:
22033521
PMCID:
PMC3281757
DOI:
10.1126/science.1213210
[Indexed for MEDLINE]
Free PMC Article

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