Biotechnology and Molecular Biology Reviews

  • Abbreviation: Biotechnol. Mol. Biol. Rev.
  • Language: English
  • ISSN: 1538-2273
  • DOI: 10.5897/BMBR
  • Start Year: 2006
  • Published Articles: 101

Review

Probing yeast for insights into neurodegenerative disease: ORFeome-wide screens for genetic modifiers of α-synuclein cytotoxicity

Richard A. Manfready1,2
1 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. 2Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Email: [email protected]

  •  Accepted: 07 July 2010
  •  Published: 31 October 2010

Abstract

Several of the most devastating neurodegenerative disorders, including Parkinson’s disease and dementia with Lewy bodies, belong to the synucleinopathy class of common neural disorders. A synucleinopathy is characterized by brain tissue plaques formed by the aggregation of misfolded protein―mainly misfolded α-synuclein. α-Synuclein has been extensively studied as the primary protein aggregate in brains afflicted by Parkinson’s disease, but the toxic mechanism in which it is involved remains largely enigmatic. Fortunately, a simple but innovative yeast model of synucleinopathy has made possible high-throughput screens for genetic modifiers of α-synuclein toxicity. Deftly interpreted through the use of computational algorithms, these screens could reveal the genetic regulatory networks that underlie synuclein toxicity in vivo, and may enable therapeutic strategies to target the genetic root of neurodegeneration.

 

Key words: Parkinson’s disease, α-synuclein, high-throughput screen, synucleinopathy.