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Developing Yeast Models of Human Neurodegenerative Disorders

Part of the Methods in Molecular Biology book series (MIMB,volume 793)

Abstract

Neurodegenerative diseases represent one of the most devastating types of diseases in older populations in our time. Significant efforts have been made over the last 20 years to understand the molecular, biochemical, and physiological alterations underlying these diseases. However, in most cases, little is known about their pathological mechanisms due to their high complexity and involvement of a multiplicity of cellular pathways. To gain insight into this group of disorders and to devise potential therapeutic approaches, cellular and animal models of neurodegenerative proteinopathies have been created. Among them, the yeast Saccharomyces cerevisiae has been one of the most popular model organisms due to the degree of conservation of many biological pathways from yeast to human as well as its ease of use. Here, we describe how to create yeast models of neurodegenerative proteinopathies by ectopic expression of human proteins and how to perform a basic characterization of these models by analyzing cellular toxicity and protein aggregation.

Key words

  • Neurodegeneration
  • Proteinophaties
  • Yeast model
  • Protein aggregation

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References

  1. Botstein, D. (1991) Why yeast Hosp. Pract. (Off. Ed.) 26, 157–61.

    CAS  Google Scholar 

  2. Miller-Fleming, L., Giorgini, F., and Outeiro, T. F. (2008) Yeast as a model for studying human neurodegenerative disorders Biotechnol. J. 3, 325–38.

    PubMed  CrossRef  CAS  Google Scholar 

  3. Khurana, V., and Lindquist, S. Modelling neurodegeneration in Saccharomyces cerevisiae: why cook with baker’s yeast? Nat. Rev. Neurosci. 11, 436–49.

    Google Scholar 

  4. Middendorp, O., Luthi, U., Hausch, F., and Barberis, A. (2004) Searching for the most effective screening system to identify cell-active inhibitors of beta-secretase Biol. Chem. 385, 481–5.

    PubMed  CrossRef  CAS  Google Scholar 

  5. Caine, J., Sankovich, S., Antony, H., Waddington, L., Macreadie, P., Varghese, J., and Macreadie, I. (2007) Alzheimer’s Abeta fused to green fluorescent protein induces growth stress and a heat shock response FEMS Yeast Res. 7, 1230–6.

    CrossRef  CAS  Google Scholar 

  6. Krobitsch, S., and Lindquist, S. (2000) Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins Proc. Natl. Acad. Sci. USA 97, 1589–94.

    PubMed  CrossRef  CAS  Google Scholar 

  7. Meriin, A. B., Zhang, X., He, X., Newnam, G. P., Chernoff, Y. O., and Sherman, M. Y. (2002) Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1 J. Cell Biol. 157, 997–1004. Epub 10 June 2002.

    Google Scholar 

  8. Giorgini, F., Guidetti, P., Nguyen, Q., Bennett, S. C., and Muchowski, P. J. (2005) A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease Nat. Genet. 37, 526–31.

    PubMed  CrossRef  CAS  Google Scholar 

  9. Outeiro, T. F., and Lindquist, S. (2003) Yeast cells provide insight into alpha-synuclein biology and pathobiology Science 302, 1772–5.

    PubMed  CrossRef  CAS  Google Scholar 

  10. Chen, Q., Thorpe, J., and Keller, J. N. (2005) Alpha-synuclein alters proteasome function, protein synthesis, and stationary phase viability J. Biol. Chem. 280, 30009–17. Epub 7 June 2005.

    Google Scholar 

  11. Dixon, C., Mathias, N., Zweig, R. M., Davis, D. A., and Gross, D. S. (2005) Alpha-synuclein targets the plasma membrane via the secretory pathway and induces toxicity in yeast Genetics 170, 47–59.

    PubMed  CrossRef  CAS  Google Scholar 

  12. Johnson, B. S., McCaffery, J. M., Lindquist, S., and Gitler, A. D. (2008) A yeast TDP-43 proteinopathy model: exploring the molecular determinants of TDP-43 aggregation and cellular toxicity Proc. Natl. Acad. Sci. USA 105, 6439–44.

    PubMed  CrossRef  CAS  Google Scholar 

  13. Myers, A. M., Pape, L. K., and Tzagoloff, A. (1985) Mitochondrial protein synthesis is required for maintenance of intact mitochondrial genomes in Saccharomyces cerevisiae EMBO J. 4, 2087–92.

    PubMed  CAS  Google Scholar 

  14. Ocampo, A., and Barrientos, A. (2008) From the bakery to the brain business: developing inducible yeast models of human neurodegenerative disorders Biotechniques 45, vii–xiv.

    Google Scholar 

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Correspondence to Antoni Barrientos .

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Ocampo, A., Barrientos, A. (2011). Developing Yeast Models of Human Neurodegenerative Disorders. In: Manfredi, G., Kawamata, H. (eds) Neurodegeneration. Methods in Molecular Biology, vol 793. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-328-8_8

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  • DOI: https://doi.org/10.1007/978-1-61779-328-8_8

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-327-1

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