Studying Huntington’s Disease in Yeast: From Mechanisms to Pharmacological Approaches
Huntington’s disease (HD) is a neurodegenerative disorder that leads to progressive neuronal loss, provoking impaired motor control, cognitive decline, and dementia. So far, HD remains incurable, and available drugs are effective only for symptomatic management. HD is caused by a mutant form of the...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2018.00318/full |
| _version_ | 1831683434748051456 |
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| author | Sebastian Hofer Katharina Kainz Andreas Zimmermann Andreas Zimmermann Maria A. Bauer Tobias Pendl Michael Poglitsch Frank Madeo Frank Madeo Didac Carmona-Gutierrez |
| author_facet | Sebastian Hofer Katharina Kainz Andreas Zimmermann Andreas Zimmermann Maria A. Bauer Tobias Pendl Michael Poglitsch Frank Madeo Frank Madeo Didac Carmona-Gutierrez |
| author_sort | Sebastian Hofer |
| collection | DOAJ |
| description | Huntington’s disease (HD) is a neurodegenerative disorder that leads to progressive neuronal loss, provoking impaired motor control, cognitive decline, and dementia. So far, HD remains incurable, and available drugs are effective only for symptomatic management. HD is caused by a mutant form of the huntingtin protein, which harbors an elongated polyglutamine domain and is highly prone to aggregation. However, many aspects underlying the cytotoxicity of mutant huntingtin (mHTT) remain elusive, hindering the efficient development of applicable interventions to counteract HD. An important strategy to obtain molecular insights into human disorders in general is the use of eukaryotic model organisms, which are easy to genetically manipulate and display a high degree of conservation regarding disease-relevant cellular processes. The budding yeast Saccharomyces cerevisiae has a long-standing and successful history in modeling a plethora of human maladies and has recently emerged as an effective tool to study neurodegenerative disorders, including HD. Here, we summarize some of the most important contributions of yeast to HD research, specifically concerning the elucidation of mechanistic features of mHTT cytotoxicity and the potential of yeast as a platform to screen for pharmacological agents against HD. |
| first_indexed | 2024-12-20T06:37:37Z |
| format | Article |
| id | doaj.art-0cb749710aee4ff683f0fd3fc0641c54 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-20T06:37:37Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-0cb749710aee4ff683f0fd3fc0641c542022-12-21T19:49:56ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-09-011110.3389/fnmol.2018.00318387795Studying Huntington’s Disease in Yeast: From Mechanisms to Pharmacological ApproachesSebastian Hofer0Katharina Kainz1Andreas Zimmermann2Andreas Zimmermann3Maria A. Bauer4Tobias Pendl5Michael Poglitsch6Frank Madeo7Frank Madeo8Didac Carmona-Gutierrez9Institute of Molecular Biosciences, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaDepartment of Internal Medicine, Medical University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaBioTechMed-Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaHuntington’s disease (HD) is a neurodegenerative disorder that leads to progressive neuronal loss, provoking impaired motor control, cognitive decline, and dementia. So far, HD remains incurable, and available drugs are effective only for symptomatic management. HD is caused by a mutant form of the huntingtin protein, which harbors an elongated polyglutamine domain and is highly prone to aggregation. However, many aspects underlying the cytotoxicity of mutant huntingtin (mHTT) remain elusive, hindering the efficient development of applicable interventions to counteract HD. An important strategy to obtain molecular insights into human disorders in general is the use of eukaryotic model organisms, which are easy to genetically manipulate and display a high degree of conservation regarding disease-relevant cellular processes. The budding yeast Saccharomyces cerevisiae has a long-standing and successful history in modeling a plethora of human maladies and has recently emerged as an effective tool to study neurodegenerative disorders, including HD. Here, we summarize some of the most important contributions of yeast to HD research, specifically concerning the elucidation of mechanistic features of mHTT cytotoxicity and the potential of yeast as a platform to screen for pharmacological agents against HD.https://www.frontiersin.org/article/10.3389/fnmol.2018.00318/fullChorea Huntingtonhuntingtindrug discoverydisease modelneurodegenerationapoptosis |
| spellingShingle | Sebastian Hofer Katharina Kainz Andreas Zimmermann Andreas Zimmermann Maria A. Bauer Tobias Pendl Michael Poglitsch Frank Madeo Frank Madeo Didac Carmona-Gutierrez Studying Huntington’s Disease in Yeast: From Mechanisms to Pharmacological Approaches Frontiers in Molecular Neuroscience Chorea Huntington huntingtin drug discovery disease model neurodegeneration apoptosis |
| title | Studying Huntington’s Disease in Yeast: From Mechanisms to Pharmacological Approaches |
| title_full | Studying Huntington’s Disease in Yeast: From Mechanisms to Pharmacological Approaches |
| title_fullStr | Studying Huntington’s Disease in Yeast: From Mechanisms to Pharmacological Approaches |
| title_full_unstemmed | Studying Huntington’s Disease in Yeast: From Mechanisms to Pharmacological Approaches |
| title_short | Studying Huntington’s Disease in Yeast: From Mechanisms to Pharmacological Approaches |
| title_sort | studying huntington s disease in yeast from mechanisms to pharmacological approaches |
| topic | Chorea Huntington huntingtin drug discovery disease model neurodegeneration apoptosis |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2018.00318/full |
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