Document Detail

Polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in Spinocerebellar ataxia 7 mouse retina.
MedLine Citation:
PMID:  20600911     Owner:  NLM     Status:  In-Process    
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.
Marina G Yefimova; Nadia Messaddeq; Alice Karam; Carine Jacquard; Chantal Weber; Laurent Jonet; Uwe Wolfrum; Jean-Claude Jeanny; Yvon Trottier
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-18
Journal Detail:
Title:  Neurobiology of disease     Volume:  40     ISSN:  1095-953X     ISO Abbreviation:  Neurobiol. Dis.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  311-24     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Inc. All rights reserved.
Department of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR 7104-CNRS/INSERM/UdS, BP10142, 67404 Illkirch Cédex, France.
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