title: Overexpression of Hsp27 ameliorates symptoms of Alzheimer's disease in APP/PS1 mice.
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.
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Temesvari Ave. 62, 6726, Szeged, Hungary, toth.e.melinda@gmail.com.
authors.forename: Melinda Erzsébet
authors.initials: ME
authors.lastname: Tóth
authors.forename: Viktor
authors.initials: V
authors.lastname: Szegedi
authors.forename: Edina
authors.initials: E
authors.lastname: Varga
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
authors.forename: János
authors.initials: J
authors.lastname: Horváth
authors.forename: Emőke
authors.initials: E
authors.lastname: Borbély
authors.forename: Balázs
authors.initials: B
authors.lastname: Csibrány
authors.forename: Róbert
authors.initials: R
authors.lastname: Alföldi
authors.forename: Nikolett
authors.initials: N
authors.lastname: Lénárt
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Miklós
authors.initials: M
authors.lastname: Sántha
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D016632:Apolipoprotein A-I; D055551:HSP27 Heat-Shock Proteins; D053764:Presenilin-1