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

Result code in 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>

Alternative codes found

RIV/67985823:_____/18:00490356

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/GA16-00918S" target="_blank" >GA16-00918S: Neuroprotective effects of novel analogs of anorexigenic prolactin-releasing peptide (PrRP) in mouse models of neurodegeneration and obesity</a><br>

Continuities

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

Publication year

2018

Confidentiality

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

Name of the periodical

Journal of Alzheimer's Disease

ISSN

1387-2877

e-ISSN

—

Volume of the periodical

62

Issue of the periodical within the volume

4

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

12

Pages from-to

1725-1736

UT code for WoS article

000428855700021

EID of the result in the Scopus database

2-s2.0-85044824671