Yeast-Based Screens to Target Alpha-Synuclein Toxicity

Methods Mol Biol. 2019;1948:145-156. doi: 10.1007/978-1-4939-9124-2_12.

Abstract

The budding yeast Saccharomyces cerevisiae (S. cerevisiae) has been a remarkable experimental model for the discovery of fundamental biological processes. The high degree of conservation of cellular and molecular processes between the budding yeast and higher eukaryotes has made it a valuable system for the investigation of the molecular mechanisms behind various types of devastating human pathologies. Genetic screens in yeast provided important insight into the toxic mechanisms associated with the accumulation of misfolded proteins. Thus, using yeast genetics and high-throughput screens, novel molecular targets with therapeutic potential have been identified. Here, we describe a yeast screen protocol for the identification of genetic modifiers of alpha-synuclein (aSyn) toxicity, thereby accelerating the identification of novel potential targets for intervention in Parkinson's disease (PD) and other synucleinopathies.

Keywords: Alpha-synuclein; Genetic screens; Parkinson’s disease; Saccharomyces cerevisiae; Synucleinopathies; Yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Evaluation, Preclinical / methods*
  • High-Throughput Screening Assays*
  • Humans
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Reproducibility of Results
  • Yeasts / genetics*
  • Yeasts / metabolism
  • alpha-Synuclein / antagonists & inhibitors*
  • alpha-Synuclein / genetics*
  • alpha-Synuclein / metabolism

Substances

  • alpha-Synuclein