Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-4
pubmed:dateCreated
2003-10-3
pubmed:abstractText
Spinocerebellar ataxia type 7 (SCA7) is one member of a growing list of neurodegenerative disorders that are all caused by CAG repeat expansions that produce disease by encoding elongated polyglutamine tracts in a variety of apparently unrelated proteins. In this review, we provide an overview of our efforts to determine the molecular basis of polyglutamine neurotoxicity in SCA7 by modeling this polyglutamine repeat disorder in mice. We discuss how our SCA7 mouse model develops a phenotype that is reminiscent of the retinal and cerebellar disease pathology seen in human patients. All of these findings are considered in the context of numerous other models of polyglutamine disease pathology in mice and other organisms, together with various other in vitro and biochemical studies. We present the competing hypotheses of polyglutamine disease pathogenesis, and explain how our studies of SCA7 brainstem and retinal degeneration using this mouse model have yielded insights into possible mechanisms and pathways of polyglutamine disease pathology. In addition to illustrating how our SCA7 mouse model has allowed us to develop and advance notions of disease pathogenesis, we propose a model of polyglutamine molecular pathology that attempts to integrate the key observations in the field. We close by describing why our SCA7 mouse model should be useful for the next phase of polyglutamine disease research--the development of therapies, and predict that this stage of experimentation will continue to rely heavily on the mouse.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1424-859X
pubmed:author
pubmed:copyrightInfo
Copyright 2003 S. Karger AG, Basel
pubmed:issnType
Electronic
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
164-74
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Insights into the molecular basis of polyglutamine neurodegeneration from studies of a spinocerebellar ataxia type 7 mouse model.
pubmed:affiliation
Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98195-7110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't