Publication Date:
2011-10-29
Description:
Abeta (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Abeta 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 Abeta was previously unknown. The factors identified in yeast modified Abeta toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Abeta impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Abeta, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281757/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281757/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- F32 NS067782-02/NS/NINDS NIH HHS/ -- K08 AG034290/AG/NIA NIH HHS/ -- K08AG034290/AG/NIA NIH HHS/ -- P30 AG019610/AG/NIA NIH HHS/ -- P30AG10161/AG/NIA NIH HHS/ -- R01 AG015819/AG/NIA NIH HHS/ -- R01 AG017917/AG/NIA NIH HHS/ -- R01AG15819/AG/NIA NIH HHS/ -- R01AG17917/AG/NIA NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Dec 2;334(6060):1241-5. doi: 10.1126/science.1213210. Epub 2011 Oct 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22033521" target="_blank"〉PubMed〈/a〉
Keywords:
Alzheimer Disease/*genetics/*metabolism
;
Amyloid beta-Peptides/chemistry/genetics/*metabolism
;
Animals
;
Animals, Genetically Modified
;
Caenorhabditis elegans/cytology/genetics/metabolism
;
Cell Membrane/metabolism
;
Cells, Cultured
;
Clathrin/metabolism
;
Cytoskeleton/metabolism
;
Disease Susceptibility
;
*Endocytosis
;
Genetic Association Studies
;
Genetic Testing
;
Glutamates/metabolism
;
Humans
;
Monomeric Clathrin Assembly Proteins/genetics/metabolism
;
Neurons/physiology
;
Peptide Fragments/chemistry/genetics/*metabolism
;
Protein Multimerization
;
Protein Transport
;
Rats
;
Risk Factors
;
*Saccharomyces cerevisiae/cytology/genetics/growth & development/metabolism
;
Saccharomyces cerevisiae Proteins/genetics/metabolism
;
Secretory Pathway
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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