Polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in Spinocerebellar ataxia 7 mouse retina
In neurodegenerative disorders caused by polyglutamine (polyQ) expansion, polyQ toxicity is thought to trigger a linear cascade of successive degenerative events leading to neuronal death. To understand how neurons cope with polyQ toxicity, we studied a Spinocerebellar ataxia 7 (SCA7) mouse which ex...
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doaj-6edc4f3a318f4c6587fb525b143f74f32021-03-20T04:59:49ZengElsevierNeurobiology of Disease1095-953X2010-10-01401311324Polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in Spinocerebellar ataxia 7 mouse retinaMarina G. Yefimova0Nadia Messaddeq1Alice Karam2Carine Jacquard3Chantal Weber4Laurent Jonet5Uwe Wolfrum6Jean-Claude Jeanny7Yvon Trottier8Department of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR 7104-CNRS/INSERM/UdS, BP10142, 67404 Illkirch Cédex, France; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St-Petersburg, RussiaDepartment of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR 7104-CNRS/INSERM/UdS, BP10142, 67404 Illkirch Cédex, FranceDepartment of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR 7104-CNRS/INSERM/UdS, BP10142, 67404 Illkirch Cédex, FranceDepartment of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR 7104-CNRS/INSERM/UdS, BP10142, 67404 Illkirch Cédex, FranceDepartment of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR 7104-CNRS/INSERM/UdS, BP10142, 67404 Illkirch Cédex, FranceInserm UMRS 872 Team 17, Centre de Recherche des Cordeliers, Paris, FranceJohannes Gutenberg University of Mainz, D-55099 Mainz, GermanyInserm UMRS 872 Team 17, Centre de Recherche des Cordeliers, Paris, FranceDepartment of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR 7104-CNRS/INSERM/UdS, BP10142, 67404 Illkirch Cédex, France; Corresponding author. Fax: +33 3 88653201.In neurodegenerative disorders caused by polyglutamine (polyQ) expansion, polyQ toxicity is thought to trigger a linear cascade of successive degenerative events leading to neuronal death. To understand how neurons cope with polyQ toxicity, we studied a Spinocerebellar ataxia 7 (SCA7) mouse which expresses polyQ-expanded ATXN7 only in rod photoreceptors. We show that in response to polyQ toxicity, SCA7 rods go through a range of radically different cell fates, including apoptotic and non-apoptotic cell death, cell migration, morphological transformation into a round cell or, most remarkably, cell division. The temporal profile of retinal remodeling indicates that some degenerative pathways are triggered early in the disease but decline later on, while others worsen progressively. Retinal remodeling results in a relative maintenance of photoreceptor population, but does not preserve the retinal function. Rod responses to proteotoxicity correlate with the nature, level and ratio of mutant ATXN7 species. The multifaceted response of neurons to polyQ toxicity is an important concept for the design of therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S0969996110002019PolyglutamineNeurodegenerationSpinocerebellar ataxia 7PhotoreceptorProliferationRemodeling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marina G. Yefimova Nadia Messaddeq Alice Karam Carine Jacquard Chantal Weber Laurent Jonet Uwe Wolfrum Jean-Claude Jeanny Yvon Trottier |
spellingShingle |
Marina G. Yefimova Nadia Messaddeq Alice Karam Carine Jacquard Chantal Weber Laurent Jonet Uwe Wolfrum Jean-Claude Jeanny Yvon Trottier Polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in Spinocerebellar ataxia 7 mouse retina Neurobiology of Disease Polyglutamine Neurodegeneration Spinocerebellar ataxia 7 Photoreceptor Proliferation Remodeling |
author_facet |
Marina G. Yefimova Nadia Messaddeq Alice Karam Carine Jacquard Chantal Weber Laurent Jonet Uwe Wolfrum Jean-Claude Jeanny Yvon Trottier |
author_sort |
Marina G. Yefimova |
title |
Polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in Spinocerebellar ataxia 7 mouse retina |
title_short |
Polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in Spinocerebellar ataxia 7 mouse retina |
title_full |
Polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in Spinocerebellar ataxia 7 mouse retina |
title_fullStr |
Polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in Spinocerebellar ataxia 7 mouse retina |
title_full_unstemmed |
Polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in Spinocerebellar ataxia 7 mouse retina |
title_sort |
polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in spinocerebellar ataxia 7 mouse retina |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2010-10-01 |
description |
In neurodegenerative disorders caused by polyglutamine (polyQ) expansion, polyQ toxicity is thought to trigger a linear cascade of successive degenerative events leading to neuronal death. To understand how neurons cope with polyQ toxicity, we studied a Spinocerebellar ataxia 7 (SCA7) mouse which expresses polyQ-expanded ATXN7 only in rod photoreceptors. We show that in response to polyQ toxicity, SCA7 rods go through a range of radically different cell fates, including apoptotic and non-apoptotic cell death, cell migration, morphological transformation into a round cell or, most remarkably, cell division. The temporal profile of retinal remodeling indicates that some degenerative pathways are triggered early in the disease but decline later on, while others worsen progressively. Retinal remodeling results in a relative maintenance of photoreceptor population, but does not preserve the retinal function. Rod responses to proteotoxicity correlate with the nature, level and ratio of mutant ATXN7 species. The multifaceted response of neurons to polyQ toxicity is an important concept for the design of therapeutic strategies. |
topic |
Polyglutamine Neurodegeneration Spinocerebellar ataxia 7 Photoreceptor Proliferation Remodeling |
url |
http://www.sciencedirect.com/science/article/pii/S0969996110002019 |
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