Molecular genetics approaches in yeast to study amyloid diseases.
The occurrence of protein aggregates in ordered fibrillar structures known as amyloid, found inside and outside of brain cells, is a feature shared by many neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's diseases. Although the molecular mechanisms that underlie neurodegeneration will ultimately have to be tested in neuronal and animal models, there are several distinct advantages in using model organisms to elucidate fundamental aspects of protein aggregation, amyloid formation, and toxicity. Here, we review recent studies indicating that amyloid formation by disease-causing proteins can be faithfully recapitulated in simple yeast-based models in Saccharomyces cerevisiae. These studies have already contributed to our basic understanding of molecular chaperone function/dysfunction in Huntington's disease, and functional genomics approaches being undertaken currently will likely bear novel insights into the genes and pathways that modulate neuronal cell dysfunction and death in these devastating diseases. A final advantage of using yeast to study amyloid formation and toxicity is the ease and rapidity with which large-scale drug-screening efforts can be conducted in this model organism.
Outeiro
Tiago Fleming
TF
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. outeiro@wi.mit.edu
Muchowski
Paul J
PJ
D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D008967:Molecular Biology / Q000639:trends*; D018832:Molecular Chaperones / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D058225:Plaque, Amyloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017510:Protein Folding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
D018832:Molecular Chaperones; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins