Novel Lipidized Analog of Prolactin-Releasing Peptide Improves Memory Impairment and Attenuates Hyperphosphorylation of Tau Protein in a Mouse Model of Tauopathy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00490184" target="_blank" >RIV/61388963:_____/18:00490184 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/18:00490356

Výsledek na webu

<a href="http://dx.doi.org/10.3233/JAD-171041" target="_blank" >http://dx.doi.org/10.3233/JAD-171041</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3233/JAD-171041" target="_blank" >10.3233/JAD-171041</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel Lipidized Analog of Prolactin-Releasing Peptide Improves Memory Impairment and Attenuates Hyperphosphorylation of Tau Protein in a Mouse Model of Tauopathy

Popis výsledku v původním jazyce

Obesity and type 2 diabetes mellitus (T2DM) were characterized as risk factors for Alzheimer's disease (AD) development. Subsequently, T2DM drugs, such as liraglutide, were proven to be neuroprotective compounds attenuating levels of amyloid deposits, and tau hyperphosphorylation, both hallmarks of AD. The central anorexigenic effects of liraglutide inspired us to examine the potential neuroprotective effects of palm(11)-PrRP31, a strong anorexigenic analog with glucose-lowering properties, in THY-Tau22 mice overexpressing mutated human tau, a model of AD-like tau pathology. Seven-month-old THY-Tau22 mice were subcutaneously infused with palm(11)-PrRP31 for 2 months. Spatial memory was tested before and after the treatment, using a Y-maze. At the end of the treatment, mice were sacrificed by decapitation and hippocampi were dissected and analyzed by immunoblotting with specific antibodies. Treatment with palm(11)-PrRP31 resulted in significantly improved spatial memory. In the hippocampi of palm(11)-PrRP31-treated THY-Tau22 mice, tau protein phosphorylation was attenuated at Thr231, Ser396, and Ser404, the epitopes linked to AD progression. The mechanism of this attenuation remains unclear, since the activation of those kinases most implicated in tau hyperphosphorylation, such as GSK-3 beta, JNK, or MAPK/ERK1/2, remained unchanged by palm(11)-PrRP31 treatment. Furthermore, we observed a significant increase in the amount of postsynaptic density protein PSD95, and a non-significant increase of synaptophysin, both markers of increased synaptic plasticity, which could also result in improved spatial memory of THY-Tau22 mice treated with palm(11)-PrRP31. Palm(11)-PrRP31 seems to be a potential tool for the attenuation of neurodegenerative disorders in the brain. However, the exact mechanism of its action must be elucidated.

Název v anglickém jazyce

Novel Lipidized Analog of Prolactin-Releasing Peptide Improves Memory Impairment and Attenuates Hyperphosphorylation of Tau Protein in a Mouse Model of Tauopathy

Popis výsledku anglicky

Obesity and type 2 diabetes mellitus (T2DM) were characterized as risk factors for Alzheimer's disease (AD) development. Subsequently, T2DM drugs, such as liraglutide, were proven to be neuroprotective compounds attenuating levels of amyloid deposits, and tau hyperphosphorylation, both hallmarks of AD. The central anorexigenic effects of liraglutide inspired us to examine the potential neuroprotective effects of palm(11)-PrRP31, a strong anorexigenic analog with glucose-lowering properties, in THY-Tau22 mice overexpressing mutated human tau, a model of AD-like tau pathology. Seven-month-old THY-Tau22 mice were subcutaneously infused with palm(11)-PrRP31 for 2 months. Spatial memory was tested before and after the treatment, using a Y-maze. At the end of the treatment, mice were sacrificed by decapitation and hippocampi were dissected and analyzed by immunoblotting with specific antibodies. Treatment with palm(11)-PrRP31 resulted in significantly improved spatial memory. In the hippocampi of palm(11)-PrRP31-treated THY-Tau22 mice, tau protein phosphorylation was attenuated at Thr231, Ser396, and Ser404, the epitopes linked to AD progression. The mechanism of this attenuation remains unclear, since the activation of those kinases most implicated in tau hyperphosphorylation, such as GSK-3 beta, JNK, or MAPK/ERK1/2, remained unchanged by palm(11)-PrRP31 treatment. Furthermore, we observed a significant increase in the amount of postsynaptic density protein PSD95, and a non-significant increase of synaptophysin, both markers of increased synaptic plasticity, which could also result in improved spatial memory of THY-Tau22 mice treated with palm(11)-PrRP31. Palm(11)-PrRP31 seems to be a potential tool for the attenuation of neurodegenerative disorders in the brain. However, the exact mechanism of its action must be elucidated.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/GA16-00918S" target="_blank" >GA16-00918S: Neuroprotektivní účinky nových analogů anorektického peptidu uvolňujícího prolaktin (PrRP) v myších modelech neurodegenerace a obezity</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Alzheimer's Disease

ISSN

1387-2877

e-ISSN

—

Svazek periodika

62

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

1725-1736

Kód UT WoS článku

000428855700021

EID výsledku v databázi Scopus

2-s2.0-85044824671