ALS (amyotrophic lateral sclerosis) is a fatal neurodegenerative disease attributable to the death of motor neurons. Associated with ALS are mutations in the genes encoding SOD1 (superoxide dismutase 1), FUS (fused in Sarcoma) protein and TDP-43 (TAR DNA-binding protein-43) each of which leads to aggregation of the respective protein. For example, the ALS-associated mutations in the hSOD1 (human SOD1) gene typically destabilize the native SOD homodimer, leading to misfolding, aggregation and degradation of SOD1. The ALS-associated pathology is not a consequence of the functional inactivation of SOD1 itself, but is rather due to a toxic gain-of-function triggered by mutant SOD1. Recently, the molecular basis of a number of human neurodegenerative diseases resulting from protein misfolding and aggregation, including fALS (familial ALS), was probed by using the baker's yeast, Saccharomyces cerevisiae, as a highly tractable model. Such studies have, for example, identified novel mutant SOD1-specific interactions and demonstrated that mutant SOD1 disrupts mitochondrial homoeostasis. Features of ALS associated with TDP-43 aggregation have also been recapitulated in S. cerevisiae including the identification of modulators of the toxicity of TDP-43. In this paper, we review recent studies of ALS pathogenesis using S. cerevisiae as a model organism and summarize the potential mechanisms involved in ALS progression.
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October 2011
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Conference Article|
September 21 2011
Using yeast models to probe the molecular basis of amyotrophic lateral sclerosis
Emma L. Bastow;
Emma L. Bastow
1School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, U.K.
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Campbell W. Gourlay;
Campbell W. Gourlay
1
1School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, U.K.
1Correspondence may be addressed to either of these authors (email M.F.Tuite@kent.ac.uk and C.W.Gourlay@kent.ac.uk).
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Mick F. Tuite
Mick F. Tuite
1
1School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, U.K.
1Correspondence may be addressed to either of these authors (email M.F.Tuite@kent.ac.uk and C.W.Gourlay@kent.ac.uk).
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Publisher: Portland Press Ltd
Received:
June 30 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (5): 1482–1487.
Article history
Received:
June 30 2011
Citation
Emma L. Bastow, Campbell W. Gourlay, Mick F. Tuite; Using yeast models to probe the molecular basis of amyotrophic lateral sclerosis. Biochem Soc Trans 1 October 2011; 39 (5): 1482–1487. doi: https://doi.org/10.1042/BST0391482
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