[摘要]：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.
