Harnessing the power of yeast to unravel the molecular basis of neurodegeneration

© 2013 International Society for NeurochemistrySeveral neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), or prion diseases, are known for their intimate association with protein misfolding and aggregation. These disorders are characterized by the loss of specific neuronal populations in the brain and are highly associated with aging, suggesting a decline in proteostasis capacity may contribute to pathogenesis. Nevertheless, the precise molecular mechanisms that lead to the selective demise of neurons remain poorly understood. As a consequence, appropriate therapeutic approaches and effective treatments are largely lacking. The development of cellular and animal models that faithfully reproduce central aspects of neurodegeneration has been crucial for advancing our understanding of these diseases. Approaches involving the sequential use of different model systems, starting with simpler cellular models and ending with validation in more complex animal models, resulted in the discovery of promising therapeutic targets and small molecules with therapeutic potential. Within this framework, the simple and well-characterized eukaryote Saccharomyces cerevisiae, also known as budding yeast, is being increasingly used to study the molecular basis of several neurodegenerative disorders. Yeast provides an unprecedented toolbox for the dissection of complex biological processes and pathways. Here, we summarize how yeast models are adding to our current understanding of several neurodegenerative disorders.This study was supported by Fundação para a Ciência e Tecnologia projects PTDC/SAU-NEU/105215/2008 and PTDC/BIA-BCM/117975/2010, and post-doctoral fellowship SFRH/BPD/35767/2007 (ST). TFO was supported by an EMBO Installation Grant and by the DFG Cluster of Excellence Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB). SA is supported by the Max Planck Society and MCM by a fellowship from the Dresden International Graduate School for Biomedicine and Bioengineering (DIGS-BB).