Triptolide T10 enhances AAV-mediated gene transfer in mice striatum

Neurosci Lett. 2010 Aug 2;479(3):187-91. doi: 10.1016/j.neulet.2010.05.046. Epub 2010 May 20.

Abstract

Adeno-associated virus (AAV) mediated gene transfer has been demonstrated to be an effective approach for treating Parkinson's disease (PD). Triptolide T10 is a monomeric compound isolated from tripterygium wilfordii Hook.f. (Thunder God vine), a traditional Chinese herb for anti-inflammatory medications. In the present study, we co-administered T10 with recombinant AAV2 in SH-SY5Y human neuroblastoma cells and in the striatum of C57BL/6 mice, and then evaluated the AAV-mediated gene expression levels. The results have shown that T10 significantly augmented the expression of AAV-mediated gene in a dose-dependent fashion without detectable cytotoxicity. As growing evidence indicated that inflammation contributed to the progression of PD, and the anti-inflammatory effect of T10 was shown in our previous studies, our data of T10 to enhance AAV transduction suggest that T10 might be potentially used as a facilitating reagent for the AAV gene therapy applications in neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dependovirus / genetics*
  • Diterpenes / pharmacology*
  • Drugs, Chinese Herbal / pharmacology
  • Epoxy Compounds / pharmacology
  • Gene Transfer Techniques*
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents / pharmacology*
  • Phenanthrenes / pharmacology*
  • Transduction, Genetic
  • Transgenes*

Substances

  • Anti-Inflammatory Agents
  • Diterpenes
  • Drugs, Chinese Herbal
  • Epoxy Compounds
  • Neuroprotective Agents
  • Phenanthrenes
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • triptolide
  • Luciferases