Overexpression of Hsp27 ameliorates symptoms of Alzheimer's disease in APP/PS1 mice

Cell Stress Chaperones. 2013 Nov;18(6):759-71. doi: 10.1007/s12192-013-0428-9. Epub 2013 Apr 21.


Hsp27 belongs to the small heat shock protein family, which are ATP-independent chaperones. The most important function of Hsp27 is based on its ability to bind non-native proteins and inhibit the aggregation of incorrectly folded proteins maintaining them in a refolding-competent state. Additionally, it has anti-apoptotic and antioxidant activities. To study the effect of Hsp27 on memory and synaptic functions, amyloid-β (Aβ) accumulation, and neurodegeneration, we generated transgenic mice overexpressing human Hsp27 protein and crossed with APPswe/PS1dE9 mouse strain, a mouse model of Alzheimer's disease (AD). Using different behavioral tests, we found that spatial learning was impaired in AD model mice and was rescued by Hsp27 overexpression. Electrophysiological recordings have revealed that excitability of neurons was significantly increased, and long-term potentiation (LTP) was impaired in AD model mice, whereas they were normalized in Hsp27 overexpressing AD model mice. Using anti-amyloid antibody, we counted significantly less amyloid plaques in the brain of APPswe/PS1dE9/Hsp27 animals compared to AD model mice. These results suggest that overexpression of Hsp27 protein might ameliorate certain symptoms of AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Apolipoprotein A-I / metabolism
  • Behavior, Animal
  • Brain / metabolism
  • Disease Models, Animal
  • HSP27 Heat-Shock Proteins / genetics
  • HSP27 Heat-Shock Proteins / metabolism*
  • Hippocampus / physiology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism*


  • Amyloid beta-Protein Precursor
  • Apolipoprotein A-I
  • HSP27 Heat-Shock Proteins
  • Presenilin-1