RGD Reference Report - 1-methyl-4-phenylpyridinium neurotoxicity is attenuated by adenoviral gene transfer of human Cu/Zn superoxide dismutase. - Rat Genome Database

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1-methyl-4-phenylpyridinium neurotoxicity is attenuated by adenoviral gene transfer of human Cu/Zn superoxide dismutase.

Authors: Barkats, M  Horellou, P  Colin, P  Millecamps, S  Faucon-Biguet, N  Mallet, J 
Citation: Barkats M, etal., J Neurosci Res. 2006 Feb 1;83(2):233-42.
RGD ID: 8655933
Pubmed: PMID:16353238   (View Abstract at PubMed)
DOI: DOI:10.1002/jnr.20696   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinson's disease treatmentIMP 8655933human gene in a rat modelRGD 
Parkinson's disease treatmentISOSOD1 (Homo sapiens)8655933; 8655933human gene in a rat modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Sod1  (superoxide dismutase 1)

Genes (Mus musculus)
Sod1  (superoxide dismutase 1, soluble)

Genes (Homo sapiens)
SOD1  (superoxide dismutase 1)


Additional Information