0 212

Cited 0 times in

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

Authors
 U J Kang  ;  W Y Lee  ;  J W Chang 
Citation
 HUMAN CELL, Vol.14(1) : 39-48, 2001 
Journal Title
 HUMAN CELL 
ISSN
 0914-7470 
Issue Date
2001
MeSH
Animals ; Aromatic-L-Amino-Acid Decarboxylases/genetics ; Disease Models, Animal ; Dopamine/biosynthesis* ; GTP Cyclohydrolase/genetics ; Gene Transfer Techniques ; Genetic Therapy* ; Humans ; Membrane Glycoproteins/genetics ; Membrane Transport Proteins* ; Neuropeptides* ; Parkinson Disease/genetics* ; Parkinson Disease/therapy* ; Rats ; Tyrosine 3-Monooxygenase/genetics ; Vesicular Biogenic Amine Transport Proteins ; Vesicular Monoamine Transport Proteins
Abstract
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.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Chang, Jin Woo(장진우) ORCID logo https://orcid.org/0000-0002-2717-0101
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142701
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links