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

Authors

  • Sandra Tenreiro,

    1. Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
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    • These authors contributed equally to this study.
  • Matthias C. Munder,

    1. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
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    • These authors contributed equally to this study.
  • Simon Alberti,

    Corresponding author
    1. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    • Address correspondence and reprint requests to Dr. Tiago Fleming Outeiro, Department of NeuroDegeneration and Restorative Research, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Goettingen, Waldweg 33, 37073 Goettingen, Germany. E-mail: tiago.outeiro@med.uni-goettingen.de or Dr. Simon Alberti, Max-Planck-Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01309 Dresden, Germany. E-mail: alberti@mpi-cbg.de

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  • Tiago F. Outeiro

    Corresponding author
    1. Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
    2. Instituto de Fisiologia, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
    3. Department of NeuroDegeneration and Restorative Research, University Medizin Göttingen, Göttingen, Germany
    • Address correspondence and reprint requests to Dr. Tiago Fleming Outeiro, Department of NeuroDegeneration and Restorative Research, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Goettingen, Waldweg 33, 37073 Goettingen, Germany. E-mail: tiago.outeiro@med.uni-goettingen.de or Dr. Simon Alberti, Max-Planck-Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01309 Dresden, Germany. E-mail: alberti@mpi-cbg.de

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Abstract

Several 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.

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