Saccharomyces cerevisiae in neuroscience: how unicellular organism helps to better understand prion protein?

Abstract

The baker’s yeast Saccharomyces (S.) cerevisiae is a single-celled eukaryotic model organism widely used in research on life sciences. Being a unicellular organism, S. cerevisiae has some evident limitations in application to neuroscience. However, yeast prions are extensively studied and they are known to share some hallmarks with mammalian prion protein or other amyloidogenic proteins found in the pathogenesis of Alzheimer’s, Parkinson’s, or Huntington’s diseases. Therefore, the yeast S. cerevisiae has been widely used for basic research on aggregation properties of proteins in cellulo and on their propagation. Recently, a yeast-based study revealed that some regions of mammalian prion protein and amyloid β 1–42 are capable of induction and propagation of yeast prions. It is one of the examples showing that evolutionarily distant organisms share common mechanisms underlying the structural conversion of prion proteins making yeast cells a useful system for studying mammalian prion protein. S. cerevisiae has also been used to design novel screening systems for anti-prion compounds from chemical libraries. Yeast-based assays are cheap in maintenance and safe for the researcher, making them a very good choice to perform preliminary screening before further characterization in systems engaging mammalian cells infected with prions. In this review, not only classical red/white colony assay but also yeast-based screening assays developed during last year are discussed. Computational analysis and research carried out using yeast prions force us to expect that prions are widely present in nature. Indeed, the last few years brought us several examples indicating that the mammalian prion protein is no more peculiar protein – it seems that a better understanding of prion proteins nature-wide may aid us with the treatment of prion diseases and other amyloid-related medical conditions.

Extracellular Vesicles-Encapsulated Yeast Prions and What They Can Tell Us about the Physical Nature of Propagons

“…Heterologous expression of pathological human proteins in yeast allows the recapitulation of most of their aggregation and cytotoxic properties. Furthermore, known modifiers of protein aggregation, such as molecular chaperones or proteolytic systems, are conserved in yeast and are able to act on these prion proteins [ 43 , 116 , 117 , 118 ]. Yeast offers a vast array of fast and cost-effective experimental possibilities, including but not limited to the availability of genome-wide deletion and mutant libraries or automated high-throughput drug screening.…”

Alzheimer’s Disease: Significant Benefit from the Yeast-Based Models

“…In addition to that, the oligomerization process is inhibited by the deletion of Hsp104 [ 134 ]. Furthermore, yeasts were also used to design novel screening systems for anti-prion compounds from chemical libraries [ 135 ].…”

Yeast as a Model to Find New Drugs and Drug Targets for VPS13-Dependent Neurodegenerative Diseases

“…cerevisiae yeast, despite a simple, unicellular structure, is widely used for studying human diseases. Yeast models of neurodegenerative diseases [12,16,17], mitochondrial dysfunctions [18][19][20], metabolic disorders [21], ageing [16,22,23], prion diseases [24,25] or even cancer [26] were established. Modelling diseases in yeast is possible due to the evolutionary conservation of cellular physiology among eukaryotes [23,27] as well as the presence of homologous genes in human and yeast genomes-more than 6600 human genes have a corresponding yeast homologue [28], and some of them complement mutations in matching yeast genes.…”