van Ham, T.J., Breitling, R. , Swertz, M. and Nollen, E.A.A. (2009) Neurodegenerative diseases: lessons from genome-wide screens in small model organisms. EMBO Molecular Medicine, 1(8-9), pp. 360-370. (doi: 10.1002/emmm.200900051)
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Abstract
Various age-related neurodegenerative diseases, including Parkinson's disease, polyglutamine expansion diseases and Alzheimer's disease, are associated with the accumulation of misfolded proteins in aggregates in the brain. How and why these proteins form aggregates and cause disease is still poorly understood. Small model organisms - the baker's yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster - have been used to model these diseases and high-throughput genetic screens using these models have led to the identification of a large number of genes that modify aggregation and toxicity of the disease proteins. In this review, we revisit these models and provide a comprehensive comparison of the genetic screens performed so far. Our integrative analysis highlights alterations of a wide variety of basic cellular processes. Not all disease proteins are influenced by alterations in the same cellular processes and despite the unifying theme of protein misfolding and aggregation, the pathology of each of the age-related misfolding disorders can be induced or influenced by a disease-protein-specific subset of molecular processes.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Breitling, Professor Rainer |
| Authors: | van Ham, T.J., Breitling, R., Swertz, M., and Nollen, E.A.A. |
| Subjects: | R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry Q Science > QH Natural history > QH301 Biology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | EMBO Molecular Medicine |
| ISSN: | 1757-4676 |
| ISSN (Online): | 1757-4684 |
| Published Online: | 26 November 2009 |
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