Treatment with a Ginkgo biloba extract, EGb 761, inhibits excitotoxicity in an animal model of spinocerebellar ataxia type 17

Drug Des Devel Ther. 2016 Feb 18;10:723-31. doi: 10.2147/DDDT.S98156. eCollection 2016.

Abstract

Spinocerebellar ataxia type 17 (SCA 17) is a polyglutamine disease caused by the expansion of CAG/CAA repeats in the TATA box-binding protein (TBP) gene. The Ginkgo biloba extract, EGb 761, contains flavonoids and terpenoids with a potential use for the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The neuroprotective effects of EGb 761 are obvious, but whether the EGb 761 has therapeutic effects in SCA 17 is still unclear. To manage our issues, we have generated TBP/79Q-expressing SH-SY5Y cells and SCA 17 transgenic mice with the mutant hTBP gene. In in vitro experiment, we observed that the EGb 761 treatment decreased the amount of sodium dodecyl sulfate-insoluble proteins in the TBP/79Q-expressing SH-SY5Y cells. We further found that the EGb 761 treatment could inhibit excitotoxicity and calcium influx and reduce the expression of apoptotic markers in glutamate-treated SH-SY5Y neuroblastoma cells. In in vivo experiment, we observed that the EGb 761 treatment (100 mg/kg intraperitoneal injection per day) could relieve the motor deficiencies of the SCA 17 transgenic mice. Our findings provide evidence that the EGb 761 treatment can be a remedy for SCA 17 via suppressing excitotoxicity and apoptosis in SCA 17 cell and animal models. Therefore, we suggest that EGb 761 may be a potential therapeutic agent for treating SCA 17.

Keywords: EGb 761; apoptosis; excitotoxicity; polyQ diseases; spinocerebellar ataxia type 17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Calcium / metabolism
  • Cell Line, Tumor
  • Disease Models, Animal
  • Glutamic Acid / pharmacology
  • Humans
  • Mice
  • Mice, Transgenic
  • Plant Extracts / therapeutic use*
  • Spinocerebellar Ataxias / drug therapy*
  • Spinocerebellar Ataxias / metabolism
  • Spinocerebellar Ataxias / pathology

Substances

  • Plant Extracts
  • Ginkgo biloba extract
  • Glutamic Acid
  • Calcium

Supplementary concepts

  • Spinocerebellar Ataxia 17