Liraglutide and a lipidized analog of prolactin-releasing peptide show neuroprotective effects in a mouse model of beta-amyloid pathology

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00501446" target="_blank" >RIV/61388963:_____/19:00501446 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/19:00504222 RIV/00216208:11110/19:10390014 RIV/00023001:_____/19:00077652 RIV/00064165:_____/19:10390014

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0028390818304258?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0028390818304258?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.neuropharm.2018.11.002" target="_blank" >10.1016/j.neuropharm.2018.11.002</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Liraglutide and a lipidized analog of prolactin-releasing peptide show neuroprotective effects in a mouse model of beta-amyloid pathology

Popis výsledku v původním jazyce

Obesity and type 2 diabetes mellitus (T2DM) are important risk factors for Alzheimer's disease (AD). Drugs originally developed for T2DM treatment, e.g., analog of glucagon-like peptide 1 liraglutide, have shown neuroprotective effects in mouse models of AD. We previously examined the neuroprotective properties of palm(11)-PrRP31, an anorexigenic and glucose-lowering analog of prolactin-releasing peptide, in a mouse model of AD-like Tau pathology, THY-Tau22 mice. Here, we demonstrate the neuroprotective effects of palm(11)-PrRP31 in double transgenic APP/PS1 mice, a model of AD-like beta-amyloid (A beta) pathology. The 7-8-month-old APP/PS1 male mice were subcutaneously injected with liraglutide or palm(11)-PrRP31 for 2 months. Both the liraglutide and palm(11)-PrRP31 treatments reduced the A beta plaque load in the hippo campus. Palm(11)-PrRP31 also significantly reduced hippocampal microgliosis, consistent with our observations of a reduced A beta plaque load, and reduced cortical astrocytosis, similar to the treatment with liraglutide. Palm(11)-PrRP31 also tended to increase neurogenesis, as indicated by the number of doublecortin-positive cells in the hippocampus. After the treatment with both anorexigenic compounds, we observed a significant decrease in Tau phosphorylation at Thr231, one of the first epitopes phosphorylated in AD. This effect was probably caused by elevated activity of protein phosphatase 2A subunit C, the main Tau phosphatase. Both liraglutide and palm(11)-PrRP31 reduced the levels of caspase 3, which has multiple roles in the pathogenesis of AD. Palm(11)-PrRP31 increased protein levels of the pre-synaptic marker synaptophysin, suggesting that palm(11)-PrRP31 might help preserve synapses. These results indicate that palm(11)-PrRP31 has promising potential for the treatment of neurodegenerative diseases.

Název v anglickém jazyce

Liraglutide and a lipidized analog of prolactin-releasing peptide show neuroprotective effects in a mouse model of beta-amyloid pathology

Popis výsledku anglicky

Obesity and type 2 diabetes mellitus (T2DM) are important risk factors for Alzheimer's disease (AD). Drugs originally developed for T2DM treatment, e.g., analog of glucagon-like peptide 1 liraglutide, have shown neuroprotective effects in mouse models of AD. We previously examined the neuroprotective properties of palm(11)-PrRP31, an anorexigenic and glucose-lowering analog of prolactin-releasing peptide, in a mouse model of AD-like Tau pathology, THY-Tau22 mice. Here, we demonstrate the neuroprotective effects of palm(11)-PrRP31 in double transgenic APP/PS1 mice, a model of AD-like beta-amyloid (A beta) pathology. The 7-8-month-old APP/PS1 male mice were subcutaneously injected with liraglutide or palm(11)-PrRP31 for 2 months. Both the liraglutide and palm(11)-PrRP31 treatments reduced the A beta plaque load in the hippo campus. Palm(11)-PrRP31 also significantly reduced hippocampal microgliosis, consistent with our observations of a reduced A beta plaque load, and reduced cortical astrocytosis, similar to the treatment with liraglutide. Palm(11)-PrRP31 also tended to increase neurogenesis, as indicated by the number of doublecortin-positive cells in the hippocampus. After the treatment with both anorexigenic compounds, we observed a significant decrease in Tau phosphorylation at Thr231, one of the first epitopes phosphorylated in AD. This effect was probably caused by elevated activity of protein phosphatase 2A subunit C, the main Tau phosphatase. Both liraglutide and palm(11)-PrRP31 reduced the levels of caspase 3, which has multiple roles in the pathogenesis of AD. Palm(11)-PrRP31 increased protein levels of the pre-synaptic marker synaptophysin, suggesting that palm(11)-PrRP31 might help preserve synapses. These results indicate that palm(11)-PrRP31 has promising potential for the treatment of neurodegenerative diseases.

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Neuropharmacology

ISSN

0028-3908

e-ISSN

—

Svazek periodika

144

Číslo periodika v rámci svazku

Jan

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

11

Strana od-do

377-387

Kód UT WoS článku

000454374900036

EID výsledku v databázi Scopus

2-s2.0-85057156355