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| 2. |
- Fruhmann, G., et al.
(författare)
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Yeast buddies helping to unravel the complexity of neurodegenerative disorders
- 2017
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374. ; 161, s. 288-305
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegenerative disorders have a profound effect on the quality of life of patients and their environment. However, the development of adequate therapies requires accurate understanding of the underlying disease pathogenesis. On that account, yeast models can play an important role, as they enable the elucidation of the mechanisms leading to neurodegenerative disorders. Furthermore, by using so-called humanized yeast systems, the findings in yeast can be interpolated to humans. In this review, we will give an overview of the current body of knowledge on the use of yeast models with regard to Huntington's, Parkinson's and Alzheimer's disease. In addition to the results, obtained with the baker's yeast Saccharomyces cerevisiae, we also consider the existing literature on the less common but promising fission yeast Schizosaccharomyces pombe. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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| 3. |
- Zhao, Lin-Ling, 1957, et al.
(författare)
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A genome-wide imaging-based screening to identify genes involved in synphilin-1 inclusion formation in Saccharomyces cerevisiae
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Synphilin-1 is a major component of Parkinson's disease (PD) inclusion bodies implicated in PD pathogenesis. However, the machinery controlling synphilin-1 inclusion formation remains unclear. Here, we investigated synphilin-1 inclusion formation using a systematic genome-wide, high-content imaging based screening approach (HCI) in the yeast Saccharomyces cerevisiae. By combining with a secondary screening for mutants showing significant changes on fluorescence signal intensity, we filtered out hits that significantly decreased the expression level of synphilin-1. We found 133 yeast genes that didn't affect synphilin-1 expression but that were required for the formation of synphilin-1 inclusions. Functional enrichment and physical interaction network analysis revealed these genes to encode for functions involved in cytoskeleton organization, histone modification, sister chromatid segregation, glycolipid biosynthetic process, DNA repair and replication. All hits were confirmed by conventional microscopy. Complementation assays were performed with a selected group of mutants, results indicated that the observed phenotypic changes in synphilin-1 inclusion formation were directly caused by the loss of corresponding genes of the deletion mutants. Further growth assays of these mutants showed a significant synthetic sick effect upon synphilin-1 expression, which supports the hypothesis that matured inclusions represent an end stage of several events meant to protect cells against the synphilin-1 cytotoxicity.
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| 4. |
- Zheng, Ju, et al.
(författare)
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A Mitochondria-Associated Oxidative Stress Perspective on Huntington's Disease
- 2018
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Ingår i: Frontiers in Molecular Neuroscience. - : Frontiers Media SA. - 1662-5099. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is genetically caused by mutation of the Huntingtin (HTT) gene. At present, the mechanisms underlying the defect of HTT and the development of HD remain largely unclear. However, increasing evidence shows the presence of enhanced oxidative stress in HD patients. In this review article, we focus on the role of oxidative stress in the pathogenesis of HD and discuss mediators and potential mechanisms involved in mutant HTT-mediated oxidative stress generation and progression. Furthermore, we emphasize the role of the unicellular organism Saccharomyces cerevisiae in investigating mutant HTT-induced oxidative stress. Overall, this review article provides an overview of the latest findings regarding oxidative stress in HD and potential therapeutic targets for HD.
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| 5. |
- Zheng, Ju, et al.
(författare)
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Role of the ribosomal quality control machinery in nucleocytoplasmic translocation of polyQ-expanded huntingtin exon-1
- 2017
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 493:1, s. 708-717
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Tidskriftsartikel (refereegranskat)abstract
- The subcellular localization of polyQ-expanded huntingtin exon1 (Httex1) modulates polyQ toxicity in models of Huntington's disease. Using genome-wide screens in a yeast model system, we report that the ribosome quality control (RQC) machinery, recently implicated in neurodegeneration, is a key determinant for the nucleocytoplasmic distribution of Httex1-103Q, Deletion of the RQC genes, LTN1 or RQC1, caused the accumulation of Httex1-103Q in the nucleus through a process that required the CAT-tail tagging activity of Rqc2 and transport via the nuclear pore complex. We provide evidence that nuclear accumulation of Httex1-103Q enhances its cytotoxicity, suggesting that the RQC machinery plays an important role in protecting cells against the adverse effects of polyQ expansion proteins. (C) 2017 The Authors. Published by Elsevier Inc.
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