학술논문
Functional links between A[beta] toxicity, endocytic trafficking, and alzheimer's disease risk factors in yeast
RESEARCH ARTICLES
RESEARCH ARTICLES
Document Type
Author abstract
Report
Report
Author
Treusch, Sebastian; Hamamichi, Shusei; Goodman, Jessica L.; Matlack, Kent E.S.; Chung, Chee Yeun; Baru, Valeriya; Shulman, Joshua M.; Parrado, Antonio; Bevis, Brooke J.; Valastyan, Julie S.; Han, Haesun; Lindhagen-Persson, Malin; Reiman, Eric M.; Evans, Denis A.; Bennett, David A.; Olofsson, Anders; DeJager, Philip L.; Tanzi, Rudolph E.; Caldwell, Kim A.; Caldwell, Guy A.; Lindquist, Susan
Source
Science. Dec 2, 2011, Vol. 334 Issue 6060, p1241, 5 p.
Subject
Language
English
ISSN
0036-8075
Abstract
A[beta] (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled A[beta] 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 A[beta] was previously unknown. The factors identified in yeast modified A[beta] toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, A[beta] impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between A[beta], endocytosis, and human AD risk factors can be ascertained with yeast as a model system. 10.1126/science.1213210