Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-25
pubmed:abstractText
Oxidative stress has been suggested to be an important mediator of dopaminergic cell death in Parkinson's disease (PD). We investigated the neuroprotective potential of Cu/Zn superoxide dismutase (SOD1) overexpression in the rat substantia nigra (SN) following adenovirus-mediated gene transfer. Human dopaminergic SK-N-SH cells were transduced with adenoviral vectors expressing either human SOD1 (Ad-SOD1) or beta-galactosidase (Ad-betagal) before exposure to 1 mM of the 1-methyl-4-phenylpyridinium ion (MPP+). A strong neuroprotective effect of SOD1 gene transfer was observed in the SK-N-SH cells exposed to MPP+ compared with controls. Adult rats were then given unilateral injections of either Ad-SOD1 or Ad-betagal into the striatum, and MPP+ was administered 8 days later at the same location. Strong transgene expression was detected in the SN dopaminergic neurons, a consequence of retrograde axonal transport of the adenoviral particles. The amphetamine-induced rotational behavior of the rats was markedly lower in Ad-SOD1-injected rats than in control animals. Also, behavioral recovery significantly correlated with the number of tyrosine hydrolase-expressing neurons in the SN of the treated rats. These results are consistent with oxidative stress contributing to the MPP+ -induced neurodegenerative process. They also indicate that SOD1 gene transfer into the nigrostriatal system may be a potential neuroprotective strategy for treating PD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0360-4012
pubmed:author
pubmed:copyrightInfo
Copyright 2005 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
233-42
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16353238-1-Methyl-4-phenylpyridinium, pubmed-meshheading:16353238-Animals, pubmed-meshheading:16353238-Cell Count, pubmed-meshheading:16353238-Cell Line, Tumor, pubmed-meshheading:16353238-Disease Models, Animal, pubmed-meshheading:16353238-Female, pubmed-meshheading:16353238-Gene Therapy, pubmed-meshheading:16353238-Gene Transfer Techniques, pubmed-meshheading:16353238-Genetic Vectors, pubmed-meshheading:16353238-Humans, pubmed-meshheading:16353238-Immunohistochemistry, pubmed-meshheading:16353238-Motor Activity, pubmed-meshheading:16353238-Neuroblastoma, pubmed-meshheading:16353238-Neurotoxicity Syndromes, pubmed-meshheading:16353238-Parkinson Disease, pubmed-meshheading:16353238-Rats, pubmed-meshheading:16353238-Rotarod Performance Test, pubmed-meshheading:16353238-Substantia Nigra, pubmed-meshheading:16353238-Superoxide Dismutase, pubmed-meshheading:16353238-Tetrazolium Salts, pubmed-meshheading:16353238-Thiazoles, pubmed-meshheading:16353238-Transgenes, pubmed-meshheading:16353238-Tyrosine 3-Monooxygenase
pubmed:year
2006
pubmed:articleTitle
1-methyl-4-phenylpyridinium neurotoxicity is attenuated by adenoviral gene transfer of human Cu/Zn superoxide dismutase.
pubmed:affiliation
Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Neurodegeneratifs (LGN), CNRS UMR 7091, Paris, France. barkats@genethon.fr
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't