Contribution of Yeast Models to Neurodegeneration Research

Abstract

As a model organism Saccharomyces cerevisiae has greatly contributed to our understanding of many fundamental aspects of cellular biology in higher eukaryotes. More recently, engineered yeast models developed to study endogenous or heterologous proteins that lay at the root of a given disease have become powerful tools for unraveling the molecular basis of complex human diseases like neurodegeneration. Additionally, with the possibility of performing target-directed large-scale screenings, yeast models have emerged as promising first-line approaches in the discovery process of novel therapeutic opportunities against these pathologies. In this paper, several yeast models that have contributed to the uncovering of the etiology and pathogenesis of several neurodegenerative diseases are described, including the most common forms of neurodegeneration worldwide, Alzheimer's, Parkinson's, and Huntington's diseases. Moreover, the potential input of these cell systems in the development of more effective therapies in neurodegeneration, through the identification of genetic and chemical suppressors, is also addressed.

Evidence of a Prion-Like Transmission of p53 Amyloid in Saccharomyces cerevisiae

“…Moreover, in the same study, we showed that p53 aggregates can be transferred from one cell to another cell, causing widespread inactivation of p53. Since infectiousness of prion-like properties, loss of function, and stable transmission from one generation to another could be suitably studied in a yeast model (46), in this report, for the first time, we established a p53 prion model in budding yeast (Fig. 12).…”

Use ofade1andade2mutations for development of a versatile red/white colour assay of amyloid-induced oxidative stress insaccharomyces cerevisiae

“…Although yeast cells lack specialized neuronal apparatus, yeast models have been extensively used for neurodegenerative diseases and have provided insights into the assembly of amyloid fibrils and their toxicity (Summers and Cyr, ). Being a eukaryote, yeast Saccharomyces cerevisiae has several conserved pathways such as cell division, transcriptional regulation, protein targeting and cytoskeletal dynamics, similar to mammals (Khurana and Lindquist, ; Pereira et al ., ). Also, the extensive understanding of molecular mechanisms of yeast prion aggregation has further helped in using yeast as a model for human amyloid diseases (Wickner, ; Khurana and Lindquist, ; Liebman and Chernoff, ; Chernoff, ; Tuite et al ., ).…”

“…A simulative aggregation of Poly‐Q‐GFP in yeast model also occurs if the number of Gln residues is >40 and this aggregation is also associated with toxicity (Meriin et al ., ). Huntingtin Poly‐Q aggregation can also alter mitochondrial morphology and compromise mitochondrial function, with early alterations in complexes II and III of the respiratory chain leading to an increase in reactive oxygen species (ROS) production (Chernoff et al ., ; Sokolov et al ., ; Solans et al ., ; Pereira et al ., ).…”

Yeast buddies helping to unravel the complexity of neurodegenerative disorders

“…A popular approach to test for prion domains is to replace Sup35p's prion domain by any given potential prion domain and to subsequently screen for growth deficient yeast cells. Many disease causing proteins were identified or confirmed to be prions through this yeast screen like β-amyloid, Huntingtin and PrP (Dong et al, 2007;Liebman and Chernoff, 2012;Pereira et al, 2012). Another process that is affected by prions, is the adaptation of yeast to poor nitrogen sources.…”