Linked Life Data

20573565

Source:http://linkedlifedata.com/resource/pubmed/id/20573565

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-8-23
pubmed:abstractText
Approximately 10% of the cases of amyotrophic lateral sclerosis (ALS) are inherited, with the majority of identified linkages in the gene encoding Cu/Zn superoxide dismutase (SOD1). Recent studies showed that human wild-type SOD1 (SOD1(WT)) overexpression accelerated disease in mice expressing human SOD1 mutants linked to ALS. However, there is a controversy whether the exacerbation mechanism occurs through coaggregation of human SOD1(WT) with SOD1 mutants, stabilization by SOD1(WT) of toxic soluble SOD1 species, or conversion of SOD1(WT) into toxic species through oxidative damage. To further address whether the exacerbation of disease requires misfolding, modifications, and/or interaction of SOD1(WT) with pathogenic forms of SOD1 species, we have studied the effect of human SOD1(WT) overexpression in mice expressing the murine mutant Sod1(G86R). Surprisingly, unlike a previous report with SOD1(G85R) mice, SOD1(WT) overexpression did not affect the life span of Sod1(G86R) mice. Our analysis of spinal cord extracts revealed a lack of heterodimerization or aggregation between human SOD1(WT) and mouse Sod1(G86R) proteins. Moreover, there was no evidence of conversion of SOD1(WT) into misfolded or abnormal SOD1 isoforms based on immunoreactivity with monoclonal antibodies specific to misfolded forms of SOD1 mutants and on analysis of SOD1 isoforms after two-dimensional gel electrophoresis. We conclude that a direct interaction between wild type and mutant forms of SOD1 is required for exacerbation of ALS disease by SOD1(WT) protein.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1095-953X
pubmed:author
pubmed:copyrightInfo
(c) 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
245-50
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Wild-type human SOD1 overexpression does not accelerate motor neuron disease in mice expressing murine Sod1 G86R.
pubmed:affiliation
Research Centre of CHUQ and Department of Psychiatry and Neuroscience, Laval University, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't