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Article: Small Interfering RNA Specific for N-Methyl-D-Aspartate Receptor 2B Offers Neuroprotection to Dopamine Neurons through Activation of MAP Kinase

TitleSmall Interfering RNA Specific for N-Methyl-D-Aspartate Receptor 2B Offers Neuroprotection to Dopamine Neurons through Activation of MAP Kinase
Authors
KeywordsExtracellular signal-regulated kinase signaling pathway
Motor symptom
N-methyl-D-aspartate receptor 2B
Parkinson's disease
Small interference RNA
Issue Date2013
PublisherS Karger AG. The Journal's web site is located at http://www.karger.com/NSG
Citation
Neurosignals, 2013, v. 21 n. 1-2, p. 42-54 How to Cite?
AbstractIn the present study, N-methyl-D-aspartate receptor 2B (NR2B)-specific siRNA was applied in parkinsonian models. Our previous results showed that reduction in expression of N-methyl-D-aspartate receptor 1 (NR1), the key subunit of N-methyl-D-aspartate receptors, by antisense oligos ameliorated the motor symptoms in the 6-hydroxydopamine (6-OHDA)-lesioned rat, an animal model of Parkinson's disease (PD) [Lai et al.: Neurochem Int 2004;45:11-22]. To further the investigation on the efficacy of gene silencing, small interference RNA (siRNA) specific for the NR2B subunit was designed and administered in the striatum of 6-OHDA-lesioned rats. The present results show that administration of NR2B-specific siRNA decreased the number of apomorphine-induced rotations in the lesioned rats and that there was a significant reduction in NR2B proteins levels after NR2B-specific siRNA administration. Furthermore, attenuation of the loss of dopaminergic neurons was found in both the striatal and substantia nigra regions of the 6-OHDA-lesioned rats that had been continuously infused with siRNA for 7 days. In addition, a significant upregulation of p-p44/42 MAPK (ERK1/2; Thr202/Tyr204) and p-CREB (Ser133) in striatal neurons was found. These results suggest that application of the gene silencing targeting NR2B could be a potential treatment of PD, and they also revealed the possibility of NR2B-specific siRNA being involved in the prosurvival pathway. Copyright © 2012 S. Karger AG, Basel.
Persistent Identifierhttp://hdl.handle.net/10722/171789
ISSN
2016 Impact Factor: 6.143
2023 SCImago Journal Rankings: 0.458
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNg, OTWen_US
dc.contributor.authorChen, LWen_US
dc.contributor.authorChan, YSen_US
dc.contributor.authorYung, KKLen_US
dc.date.accessioned2012-10-30T06:17:07Z-
dc.date.available2012-10-30T06:17:07Z-
dc.date.issued2013en_US
dc.identifier.citationNeurosignals, 2013, v. 21 n. 1-2, p. 42-54en_US
dc.identifier.issn1424-862Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/171789-
dc.description.abstractIn the present study, N-methyl-D-aspartate receptor 2B (NR2B)-specific siRNA was applied in parkinsonian models. Our previous results showed that reduction in expression of N-methyl-D-aspartate receptor 1 (NR1), the key subunit of N-methyl-D-aspartate receptors, by antisense oligos ameliorated the motor symptoms in the 6-hydroxydopamine (6-OHDA)-lesioned rat, an animal model of Parkinson's disease (PD) [Lai et al.: Neurochem Int 2004;45:11-22]. To further the investigation on the efficacy of gene silencing, small interference RNA (siRNA) specific for the NR2B subunit was designed and administered in the striatum of 6-OHDA-lesioned rats. The present results show that administration of NR2B-specific siRNA decreased the number of apomorphine-induced rotations in the lesioned rats and that there was a significant reduction in NR2B proteins levels after NR2B-specific siRNA administration. Furthermore, attenuation of the loss of dopaminergic neurons was found in both the striatal and substantia nigra regions of the 6-OHDA-lesioned rats that had been continuously infused with siRNA for 7 days. In addition, a significant upregulation of p-p44/42 MAPK (ERK1/2; Thr202/Tyr204) and p-CREB (Ser133) in striatal neurons was found. These results suggest that application of the gene silencing targeting NR2B could be a potential treatment of PD, and they also revealed the possibility of NR2B-specific siRNA being involved in the prosurvival pathway. Copyright © 2012 S. Karger AG, Basel.en_US
dc.languageengen_US
dc.publisherS Karger AG. The Journal's web site is located at http://www.karger.com/NSGen_US
dc.relation.ispartofNeuroSignalsen_US
dc.rightsNeurosignals. Copyright © S Karger AG.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectExtracellular signal-regulated kinase signaling pathway-
dc.subjectMotor symptom-
dc.subjectN-methyl-D-aspartate receptor 2B-
dc.subjectParkinson's disease-
dc.subjectSmall interference RNA-
dc.titleSmall Interfering RNA Specific for N-Methyl-D-Aspartate Receptor 2B Offers Neuroprotection to Dopamine Neurons through Activation of MAP Kinaseen_US
dc.typeArticleen_US
dc.identifier.emailChan, YS:yschan@hkucc.hku.hken_US
dc.identifier.authorityChan, YS=rp00318en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1159/000334720en_US
dc.identifier.pmid22377595-
dc.identifier.scopuseid_2-s2.0-84876141435en_US
dc.identifier.hkuros209203-
dc.identifier.hkuros216062-
dc.identifier.isiWOS:000318491000004-
dc.publisher.placeSwitzerlanden_US
dc.identifier.scopusauthoridNg, OTW=36504647100en_US
dc.identifier.scopusauthoridChen, LW=55024953600en_US
dc.identifier.scopusauthoridChan, YS=7403676627en_US
dc.identifier.scopusauthoridYung, KKL=13605496000en_US
dc.identifier.issnl1424-862X-

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