Linked Life Data

19580782

Source:http://linkedlifedata.com/resource/pubmed/id/19580782

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-7-31
pubmed:abstractText
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by degeneration of motor neurons throughout the central nervous system. Mutations of the free radical scavenging enzyme superoxide dismutase-1 (SOD1) are a cause of familial ALS but it is not known how mutations lead to cell death. Free radicals such as nitric oxide (NO) are thought to play a key pathogenic role. NO is synthesized by NO synthases (NOSs) from arginine, which is a rate-limiting factor for NO production. We found that neuronal NOS (nNOS)-positive motor neurons were depleted while inducible NOS (iNOS)-positive activated glial cells were increased in transgenic mtSOD1 (G93A) ALS mice. iNOS expression was up regulated consistent with the increases of motor neuron loss and glial activation and citrulline and NO levels while nNOS expression was decreased in G93A ALS mice. Administration of l-arginine to G93A mice reduced the severity of motor neuron depletion and glial activation. In treated animals, nNOS expression was preserved while citrulline and NO were reduced, possibly due to reduced activation of glia expressing iNOS. Our findings show that high concentrations of NO correlate with iNOS expression rather than nNOS expression in G93A ALS mice. This suggests that therapy focused on iNOS inhibition might be a fruitful direction for future ALS therapeutic trials.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
387
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
202-6
pubmed:dateRevised
2010-9-14
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Differential regulation of neuronal and inducible nitric oxide synthase (NOS) in the spinal cord of mutant SOD1 (G93A) ALS mice.
pubmed:affiliation
Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA. junghee@bu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural