Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression
Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder, characterised by progressive motor neuron degeneration and muscle paralysis. Heat shock proteins (HSPs) have significant cytoprotective properties in several models of neurodegeneration. To investigate the therapeutic potential o...
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doaj-2529ed0680444d25b6bc2a0471a5c5622021-03-20T04:55:20ZengElsevierNeurobiology of Disease1095-953X2008-04-013014255Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progressionPaul S. Sharp0Mohammed T. Akbar1Sonia Bouri2Atsushi Senda3Kieran Joshi4Han-Jou Chen5David S. Latchman6Dominic J. Wells7Jacqueline de Belleroche8Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UKDepartment of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UKDepartment of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UKDepartment of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UKDepartment of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UKDepartment of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UKBirkbeck College, University of London, Malet Street, London, WC1E 7HX, UKDepartment of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UKDepartment of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UK; Corresponding author. Fax: +44 20 8846 7099.Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder, characterised by progressive motor neuron degeneration and muscle paralysis. Heat shock proteins (HSPs) have significant cytoprotective properties in several models of neurodegeneration. To investigate the therapeutic potential of heat shock protein 27 (HSP27) in a mouse model of ALS, we conducted an extensive characterisation of transgenic mice generated from a cross between HSP27 overexpressing mice and mice expressing mutant superoxide dismutase (SOD1G93A). We report that SOD1G93A/HSP27 double transgenic mice showed delayed decline in motor strength, a significant improvement in the number of functional motor units and increased survival of spinal motor neurons compared to SOD1G93A single transgenics during the early phase of disease. However, there was no evidence of sustained neuroprotection affecting long-term survival. Marked down-regulation of HSP27 protein occurred during disease progression that was not associated with a reduction in HSP27 mRNA, indicating a translational dysfunction due to the presence of mutant SOD1 protein. This study provides further support for the therapeutic potential of HSPs in ALS and other motor neuron disorders.http://www.sciencedirect.com/science/article/pii/S0969996107002690Heat shock proteinsHeat shock protein 27HSPB1NeuroprotectionMotor neuronAmyotrophic lateral sclerosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paul S. Sharp Mohammed T. Akbar Sonia Bouri Atsushi Senda Kieran Joshi Han-Jou Chen David S. Latchman Dominic J. Wells Jacqueline de Belleroche |
spellingShingle |
Paul S. Sharp Mohammed T. Akbar Sonia Bouri Atsushi Senda Kieran Joshi Han-Jou Chen David S. Latchman Dominic J. Wells Jacqueline de Belleroche Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression Neurobiology of Disease Heat shock proteins Heat shock protein 27 HSPB1 Neuroprotection Motor neuron Amyotrophic lateral sclerosis |
author_facet |
Paul S. Sharp Mohammed T. Akbar Sonia Bouri Atsushi Senda Kieran Joshi Han-Jou Chen David S. Latchman Dominic J. Wells Jacqueline de Belleroche |
author_sort |
Paul S. Sharp |
title |
Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression |
title_short |
Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression |
title_full |
Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression |
title_fullStr |
Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression |
title_full_unstemmed |
Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression |
title_sort |
protective effects of heat shock protein 27 in a model of als occur in the early stages of disease progression |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2008-04-01 |
description |
Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder, characterised by progressive motor neuron degeneration and muscle paralysis. Heat shock proteins (HSPs) have significant cytoprotective properties in several models of neurodegeneration. To investigate the therapeutic potential of heat shock protein 27 (HSP27) in a mouse model of ALS, we conducted an extensive characterisation of transgenic mice generated from a cross between HSP27 overexpressing mice and mice expressing mutant superoxide dismutase (SOD1G93A). We report that SOD1G93A/HSP27 double transgenic mice showed delayed decline in motor strength, a significant improvement in the number of functional motor units and increased survival of spinal motor neurons compared to SOD1G93A single transgenics during the early phase of disease. However, there was no evidence of sustained neuroprotection affecting long-term survival. Marked down-regulation of HSP27 protein occurred during disease progression that was not associated with a reduction in HSP27 mRNA, indicating a translational dysfunction due to the presence of mutant SOD1 protein. This study provides further support for the therapeutic potential of HSPs in ALS and other motor neuron disorders. |
topic |
Heat shock proteins Heat shock protein 27 HSPB1 Neuroprotection Motor neuron Amyotrophic lateral sclerosis |
url |
http://www.sciencedirect.com/science/article/pii/S0969996107002690 |
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