Molecular genetics approaches in yeast to study amyloid diseases

J Mol Neurosci. 2004;23(1-2):49-60. doi: 10.1385/JMN:23:1-2:049.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Gene Expression Regulation, Fungal / genetics
  • Humans
  • Models, Biological
  • Molecular Biology / trends*
  • Molecular Chaperones / genetics
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Plaque, Amyloid / genetics*
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Protein Folding
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism


  • Molecular Chaperones
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins