The Benefits of Humanized Yeast Models to Study Parkinson’s Disease

Abstract

Over the past decade, the baker's yeast Saccharomyces cerevisiae has proven to be a useful model system to investigate fundamental questions concerning the pathogenic role of human proteins in neurodegenerative diseases such as Parkinson's disease (PD). These so-called humanized yeast models for PD initially focused on α-synuclein, which plays a key role in the etiology of PD. Upon expression of this human protein in the baker's yeast Saccharomyces cerevisiae, the events leading to aggregation and the molecular mechanisms that result in cellular toxicity are faithfully reproduced. More recently, a similar model to study the presumed pathobiology of the α-synuclein interaction partner synphilin-1 has been established. In this review we will discuss recent advances using these humanized yeast models, pointing to new roles for cell wall integrity signaling, Ca2+ homeostasis, mitophagy, and the cytoskeleton.

Yeast Cells Expressing the Human Mitochondrial DNA Polymerase Reveal Correlations between Polymerase Fidelity and Human Disease Progression

“…The "humanized" yeast system, with the yeast genes replaced by their human orthologs, has been developed to rapidly examine the pathology of human genetic variation, thanks to the powerful genetic tools available for yeast (32)(33)(34)(35). Here, we begin addressing important questions by developing "humanized" yeast expressing human mitochondrial DNA polymerase genes with wild-type and mutant alleles.…”

Modeling of molecular processes underlying Parkinson’s disease in cells of methylotrophic yeast Hansenula polymorpha

“…Modeling processes assosiated with human neurodegenerative diseases in yeasts has been already proven to be very useful to deciphering the complex mechanisms and pathways underlying these pathologies [9]. In this report we describe for the first time that methylotrophic yeast H. polymorpha can be an informative model for investigation of molecular mechanisms of PD.…”

“…Intense research has also been conducted to generate artificial models that closely resemble PD, including animal and yeast models [9]. Importantly, yeast and human cells share basic fundamental aspects of eukaryotic cell biology.…”

“…This allows a number of key processes, which are of particular interest to PD pathology, to be efficiently investigated in the well-understood yeast model. These include the mechanisms of protein folding, quality control and degradation, the components involved in the secretory pathway and vesicular trafficking, the study of mitochondrial dysfunction and oxidative stress, the mechanisms of cell death and survival [9].…”

Estudo dos efeitos da superexpressão da alfa-sinucleína sobre o tráfego mitocondrial e autofagia em leveduras, células SH-SY5Y e neurônios dopaminérgicos derivados de hiPSC de pacientes com doença de Parkinson

“…Mechanisms related to protein folding, oligomerization and aggregation can be studied in yeasts since protein quality control is conserved in these organisms (Ciaccioli et al, 2012;Khurana and Lindiquist, 2010). Therefore, yeast humanized models to study PD are also very well accepted (Franssens et a., 2013).…”