Functional Links Between Aβ Toxicity, Endocytic Trafficking, and Alzheimer’s Disease Risk Factors in Yeast
Year: 2011
Type: article
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.
Source: Science
Authors: Sebastian Treusch, Shusei Hamamichi, Jessica L. Goodman, Kent E. S. Matlack, Chee Yeun Chung, Valeriya Baru, Joshua M. Shulman, Antonio Parrado, Brooke J. Bevis, Julie S. Valastyan, Haesun Han, Malin Lindhagen-Persson, Eric M. Reiman, Denis A. Evans, David A. Bennett, Anders Olofsson, Philip L. DeJager, Rudolph E. Tanzi, Kim A. Caldwell, Guy A. Caldwell, Susan Lindquist
Institutions: Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, University of Alabama, Broad Institute, Brigham and Women's Hospital, Harvard University, Massachusetts General Hospital, Umeå University, Translational Genomics Research Institute, University of Arizona, Banner Alzheimer’s Institute, Arizona Alzheimer’s Consortium, Rush University Medical Center
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Epidemiologic Study of Neural Reserve and Neurobiology of Aging, Investigating alpha-synuclein oligomer toxicity in synucleinopathies., Exploring the Genetics of Alzheimer's Disease in Humans and Drosophila, Risk Factors, Pathology, and Clinical Expressions of AD, Rush Alzheimer's Disease Core Center, Arizona Alzheimer's Disease Core Center
OpenAlex ID: W2051629075