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

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Cell Stress and Chaperones Aims and scope

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.

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Acknowledgments

We thank S. Gonda and M. Mari for their technical assistance. This work was supported by the National Office for Research and Technology grants (TAMOP-4.2.2-08/1-2008-0002 and TAMOP-4.2.2.A-11/1/KONV-2012-0052 to B.P. and M.S., TAMOP 4.2.1B-1/9-KONV to B.P.), and OTKA PD 83581 to V.S. N.L. was a participant of the “PhD Support Program for Talented Students at University of Szeged” supported by NKTH (TAMOP-4.2.2/B-10/1-2010-0012).

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The authors declare no competing financial interests.

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Authors and Affiliations

  1. Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Temesvari Ave. 62, 6726, Szeged, Hungary

    Melinda Erzsébet Tóth, Viktor Szegedi, Balázs Csibrány, Róbert Alföldi, Nikolett Lénárt & Miklós Sántha

  2. Deparment of Medical Chemistry, Faculty of Medicine, University of Szeged, Dóm Square 11, Szeged, Hungary

    Edina Varga, Gábor Juhász, János Horváth, Emőke Borbély & Botond Penke

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  1. Melinda Erzsébet Tóth
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Correspondence to Melinda Erzsébet Tóth.

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Tóth, M.E., Szegedi, V., Varga, E. et al. Overexpression of Hsp27 ameliorates symptoms of Alzheimer's disease in APP/PS1 mice. Cell Stress and Chaperones 18, 759–771 (2013). https://doi.org/10.1007/s12192-013-0428-9

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  • DOI: https://doi.org/10.1007/s12192-013-0428-9

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