Linked Life Data

11436352

Source:http://linkedlifedata.com/resource/pubmed/id/11436352

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-7-4
pubmed:abstractText
This 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0914-7470
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39-48
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11436352-Animals, pubmed-meshheading:11436352-Aromatic-L-Amino-Acid Decarboxylases, pubmed-meshheading:11436352-Disease Models, Animal, pubmed-meshheading:11436352-Dopamine, pubmed-meshheading:11436352-GTP Cyclohydrolase, pubmed-meshheading:11436352-Gene Therapy, pubmed-meshheading:11436352-Gene Transfer Techniques, pubmed-meshheading:11436352-Humans, pubmed-meshheading:11436352-Membrane Glycoproteins, pubmed-meshheading:11436352-Membrane Transport Proteins, pubmed-meshheading:11436352-Neuropeptides, pubmed-meshheading:11436352-Parkinson Disease, pubmed-meshheading:11436352-Rats, pubmed-meshheading:11436352-Tyrosine 3-Monooxygenase, pubmed-meshheading:11436352-Vesicular Biogenic Amine Transport Proteins, pubmed-meshheading:11436352-Vesicular Monoamine Transport Proteins
pubmed:year
2001
pubmed:articleTitle
Gene therapy for Parkinson's disease: determining the genes necessary for optimal dopamine replacement in rat models.
pubmed:affiliation
Department of Neurology, University of Chicago, USA. u-kang@uchicago.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't