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Functional Links Between Aβ Toxicity, Endocytic Trafficking, and Alzheimer’s Disease Risk Factors in Yeast

Functional Links Between Aβ Toxicity, Endocytic Trafficking, and Alzheimer’s Disease Risk Factors in Yeast

Authors :
Chee Yeun Chung
Antonio R. Parrado
David A. Bennett
Sebastian Treusch
Guy A. Caldwell
Anders Olofsson
Joshua M. Shulman
Eric M. Reiman
Rudolph E. Tanzi
Denis A. Evans
Haesun Han
Susan Lindquist
Julie S. Valastyan
Valeriya Baru
Philip L. DeJager
Kent E. S. Matlack
Kim A. Caldwell
Shusei Hamamichi
Jessica L. Goodman
Brooke J. Bevis
Malin Lindhagen-Persson
Source :
Science. 334:1241-1245
Publication Year :
2011
Publisher :
American Association for the Advancement of Science (AAAS), 2011.

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.

Details

ISSN :
10959203 and 00368075
Volume :
334
Database :
OpenAIRE
Journal :
Science
Accession number :
edsair.doi.dedup.....594848704371a403f8184ef52b262667
Full Text :
https://doi.org/10.1126/science.1213210