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Gene therapy for Parkinson’s disease: determining the genes necessary for optimal dopamine replacement in rat models

DC FieldValueLanguage
dc.contributor.author장진우-
dc.date.accessioned2016-02-19T11:14:16Z-
dc.date.available2016-02-19T11:14:16Z-
dc.date.issued2001-
dc.identifier.issn0914-7470-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/142701-
dc.description.abstractThis article reviews the mechanism of dopamine delivery in the CNS in order to determine the optimal set of genes for effective gene therapy in Parkinson's disease (PD). Systematic neurobiological investigation of the biochemical steps has revealed that tyrosine hydroxylase (TH), which has been used in earlier studies, functions only when the essential cofactor, tetrahydrobiopterin (BH1) is present. Transduction of the gene for GTP cyclohydrolase I, the first and rate-limiting step in BH1 synthesis, along with the TH gene, generated cells that are capable of producing L-DOPA spontaneously both in vitro and in vivo. When the aromatic L-amino acid decarboxylase (AADC) gene was added as a third gene, in an attempt to increase the conversion of L-DOPA to dopamine, feedback inhibition by the end product, dopamine, on TH activity resulted. To circumvent this problem, we employed a complementary strategy. Gene transfer of the vesicular monoamine transporter was combined with AADC and produced genetically modified cells that can convert L-DOPA to dopamine and store it for gradual release. This approach provided a means to regulate final dopamine delivery by controlling precursor doses and to achieve more sustained delivery of dopamine. Our investigation into determining the genes necessary for optimal dopamine delivery has been facilitated by in vivo biochemical assays using microdialysis. This technique has provided us with a clear and quantitative tool to compare the effects of various genes involved in dopamine synthesis and processing.-
dc.description.statementOfResponsibilityopen-
dc.format.extent39~48-
dc.relation.isPartOfHUMAN CELL-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHAromatic-L-Amino-Acid Decarboxylases/genetics-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHDopamine/biosynthesis*-
dc.subject.MESHGTP Cyclohydrolase/genetics-
dc.subject.MESHGene Transfer Techniques-
dc.subject.MESHGenetic Therapy*-
dc.subject.MESHHumans-
dc.subject.MESHMembrane Glycoproteins/genetics-
dc.subject.MESHMembrane Transport Proteins*-
dc.subject.MESHNeuropeptides*-
dc.subject.MESHParkinson Disease/genetics*-
dc.subject.MESHParkinson Disease/therapy*-
dc.subject.MESHRats-
dc.subject.MESHTyrosine 3-Monooxygenase/genetics-
dc.subject.MESHVesicular Biogenic Amine Transport Proteins-
dc.subject.MESHVesicular Monoamine Transport Proteins-
dc.titleGene therapy for Parkinson’s disease: determining the genes necessary for optimal dopamine replacement in rat models-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Neurosurgery (신경외과학)-
dc.contributor.googleauthorU J Kang-
dc.contributor.googleauthorW Y Lee-
dc.contributor.googleauthorJ W Chang-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03484-
dc.relation.journalcodeJ01005-
dc.identifier.eissn1749-0774-
dc.identifier.pmid11436352-
dc.contributor.alternativeNameChang, Jin Woo-
dc.contributor.affiliatedAuthorChang, Jin Woo-
dc.rights.accessRightsnot available-
dc.citation.volume14-
dc.citation.number1-
dc.citation.startPage39-
dc.citation.endPage48-
dc.identifier.bibliographicCitationHUMAN CELL, Vol.14(1) : 39-48, 2001-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers

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