Title: Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse
Abstract: Annals of NeurologyVolume 47, Issue 1 p. 80-86 Original Article Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse S. J. Tabrizi MRCP, S. J. Tabrizi MRCP University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UKSearch for more papers by this authorJ. Workman BSc, J. Workman BSc University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UKSearch for more papers by this authorP. E. Hart MRCP, P. E. Hart MRCP University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UKSearch for more papers by this authorL. Mangiarini PhD, L. Mangiarini PhD Medical and Molecular Genetics, Guy's, King's and Thomas's Medical and Dental School, University College London, London, UKSearch for more papers by this authorA. Mahal PhD, A. Mahal PhD Medical and Molecular Genetics, Guy's, King's and Thomas's Medical and Dental School, University College London, London, UKSearch for more papers by this authorG. Bates PhD, G. Bates PhD Medical and Molecular Genetics, Guy's, King's and Thomas's Medical and Dental School, University College London, London, UKSearch for more papers by this authorJ. M. Cooper PhD, J. M. Cooper PhD University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UKSearch for more papers by this authorA. H. V. Schapira MD, DSc, Corresponding Author A. H. V. Schapira MD, DSc University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK Institute of Neurology, University College London, London, UKUniversity Department of Clinical Neurosciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UKSearch for more papers by this author S. J. Tabrizi MRCP, S. J. Tabrizi MRCP University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UKSearch for more papers by this authorJ. Workman BSc, J. Workman BSc University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UKSearch for more papers by this authorP. E. Hart MRCP, P. E. Hart MRCP University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UKSearch for more papers by this authorL. Mangiarini PhD, L. Mangiarini PhD Medical and Molecular Genetics, Guy's, King's and Thomas's Medical and Dental School, University College London, London, UKSearch for more papers by this authorA. Mahal PhD, A. Mahal PhD Medical and Molecular Genetics, Guy's, King's and Thomas's Medical and Dental School, University College London, London, UKSearch for more papers by this authorG. Bates PhD, G. Bates PhD Medical and Molecular Genetics, Guy's, King's and Thomas's Medical and Dental School, University College London, London, UKSearch for more papers by this authorJ. M. Cooper PhD, J. M. Cooper PhD University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UKSearch for more papers by this authorA. H. V. Schapira MD, DSc, Corresponding Author A. H. V. Schapira MD, DSc University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK Institute of Neurology, University College London, London, UKUniversity Department of Clinical Neurosciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UKSearch for more papers by this author First published: 19 April 2001 https://doi.org/10.1002/1531-8249(200001)47:1<80::AID-ANA13>3.0.CO;2-KCitations: 247AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Huntington's disease is a progressive neurodegenerative disease caused by an abnormally expanded (>36) CAG repeat within the ITI5 gene encoding a widely expressed 349-kd protein, huntingtin. The medium spiny neurons of the caudate preferentially degenerate in Huntington's disease, with the presence of neuronal intranuclear inclusions. Excitotoxicity is thought to be important in the pathogenesis of Huntington's disease; the recently described mitochondrial respiratory chain and aconitase defects in Huntington's disease brain are consistent with this hypothesis. A transgenic mouse model (R6/2) of Huntington's disease develops a movement disorder, muscle wasting, and premature death at about 14 to 16 weeks. Selective neuronal death in these mice is not seen until 14 weeks. Biochemical analysis of R6/2 mouse brain at 12 weeks demonstrated a significant reduction in aconitase and mitochondrial complex IV activities in the striatum and a decrease in complex IV activity in the cerebral cortex. Increased immunostaining for inducible nitric oxide synthase and nitrotyrosine was seen in the transgenic mouse model but not control mouse brains. These results extend the parallels between Huntington's disease and the transgenic mouse model to biochemical events and suggest complex IV deficiency and elevated nitric oxide and superoxide radical generation precede neuronal death in the R6/2 mouse and contribute to pathogenesis. Ann Neurol 2000; 47:80–86 Citing Literature Volume47, Issue1January 2000Pages 80-86 RelatedInformation
Publication Year: 2000
Publication Date: 2000-01-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 338
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