Novel disease-specific promoters for use in gene therapy for Parkinson's disease

Neurosci Lett. 2012 Nov 14;530(1):29-34. doi: 10.1016/j.neulet.2012.09.059. Epub 2012 Oct 12.

Abstract

Gene therapy is a promising therapeutic tool for Parkinson's disease (PD), but there is a lack of evaluated cell specific promoters that are relevant for the disease. We have chosen PD relevant promoter candidates for gene therapy vectors based on either previous studies; Drd1a, Drd2 and pDyn, or from a microarray study on parkinsonian patients; ACE, DNAJC3, GALNS, MAP1a and RNF25. These candidates have been evaluated in rat striatum to determine their suitability for use in cell specific vectors. The promoters had a neuronal specificity of 91-100%. The efficiency of the promoters was variable, but RNF25, DNAJC3 and MAP1a were comparable to widely used ubiquitous promoters. MAP1a was also affected by dopamine depletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chondroitinsulfatases / genetics
  • Corpus Striatum / physiology
  • Dopamine / deficiency
  • Dopaminergic Neurons / physiology
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • HSP40 Heat-Shock Proteins / genetics
  • Humans
  • Lentivirus / genetics*
  • Microtubule-Associated Proteins / genetics
  • Oligonucleotide Array Sequence Analysis
  • Parkinson Disease / genetics*
  • Parkinson Disease / therapy*
  • Peptidyl-Dipeptidase A / genetics
  • Promoter Regions, Genetic / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Ubiquitin-Protein Ligases / genetics

Substances

  • DNAJC3 protein, human
  • HSP40 Heat-Shock Proteins
  • MAP1A protein, human
  • Microtubule-Associated Proteins
  • RNF25 protein, human
  • Ubiquitin-Protein Ligases
  • Chondroitinsulfatases
  • GALNS protein, human
  • ACE protein, human
  • Peptidyl-Dipeptidase A
  • Dopamine