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

Melinda Erzsébet Tóth, Viktor Szegedi, Edina Varga, Gábor Juhász, János Horváth, Emoke Borbély, Balázs Csibrány, Róbert Alföldi, Nikolett Lénárt, Botond Penke, Miklós Sántha

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43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)759-771
Number of pages13
JournalCell Stress and Chaperones
Volume18
Issue number6
DOIs
Publication statusPublished - Apr 22 2013

Keywords

  • Alzheimer's disease
  • Amyloid plaques
  • Behavior tests
  • Electrophysiological recordings
  • Heat shock proteins
  • Mouse model
  • Real-time Q-PCR
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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  • Cite this

    Tóth, M. E., Szegedi, V., Varga, E., Juhász, G., Horváth, J., Borbély, E., Csibrány, B., Alföldi, R., Lénárt, N., Penke, B., & Sántha, M. (2013). Overexpression of Hsp27 ameliorates symptoms of Alzheimer's disease in APP/PS1 mice. Cell Stress and Chaperones, 18(6), 759-771. https://doi.org/10.1007/s12192-013-0428-9