Lentivirus-mediated APP695-RNAi reduces apoptosis in APP transgenic mouse neurons

Neuroreport. 2011 Nov 16;22(16):804-8. doi: 10.1097/WNR.0b013e32834b6c92.

Abstract

Amyloid-β peptide (Aβ) is a cleavage product of the amyloid precursor protein (APP), which is thought to be important in the pathogenesis of Alzheimer's disease (AD). Recent evidence suggests that Aβ induces neuronal apoptosis in the brain and in primary neuronal cultures. If decreased Aβ whether could reduce the neuronal apoptosis? In this study, APP695-siRNA was delivered to hippocampal and cortical neurons of APP695 transgenic mice (AD model) in vitro using a recombinant lentivirus vector. The results show that lentivirus-mediated RNA interference of the APP695 gene could reduce neuronal apoptosis, possibly through the reduction of caspase-3 activity and the neuronal apoptosis pathway. These results suggest that lentivirus-mediated RNA interference may be a potential therapeutic for AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / therapy
  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Animals, Newborn
  • Apoptosis / genetics*
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics*
  • Genetic Vectors / therapeutic use
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / pathology*
  • Neurons / virology
  • Primary Cell Culture
  • RNA Interference / physiology*

Substances

  • Amyloid beta-Protein Precursor