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

Biomedical and Life Sciences

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https://doi.org/10.1016/j.neuropharm.2018.11.002
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Keywords

Alzheimer's disease, APP/PS1 mice, Neuroinflammation, Palm11-PrRP31, Tau phosphorylation, β-amyloid plaques

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Liraglutide and a lipidized analog of prolactin-releasing peptide show neuroprotective effects in a mouse model of β-amyloid pathology. / Holubová, M.; Hrubá, L.; Popelová, A. et al.
In: Neuropharmacology, Vol. 144, 01.2019, p. 377-387.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Bibtex

@article{f00ec12f457744d3a4144de3bbd4d489,

title = "Liraglutide and a lipidized analog of prolactin-releasing peptide show neuroprotective effects in a mouse model of β-amyloid pathology",

abstract = "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 palm11-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 palm11-PrRP31 in double transgenic APP/PS1 mice, a model of AD-like β-amyloid (Aβ) pathology. The 7-8-month-old APP/PS1 male mice were subcutaneously injected with liraglutide or palm11-PrRP31 for 2 months. Both the liraglutide and palm11-PrRP31 treatments reduced the Aβ plaque load in the hippocampus. Palm11-PrRP31 also significantly reduced hippocampal microgliosis, consistent with our observations of a reduced Aβ plaque load, and reduced cortical astrocytosis, similar to the treatment with liraglutide. Palm11-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 palm11-PrRP31 reduced the levels of caspase 3, which has multiple roles in the pathogenesis of AD. Palm11-PrRP31 increased protein levels of the pre-synaptic marker synaptophysin, suggesting that palm11-PrRP31 might help preserve synapses. These results indicate that palm11-PrRP31 has promising potential for the treatment of neurodegenerative diseases. {\textcopyright} 2018 Elsevier Ltd",

keywords = "Alzheimer's disease, APP/PS1 mice, Neuroinflammation, Palm11-PrRP31, Tau phosphorylation, β-amyloid plaques",

author = "M. Holubov{\'a} and L. Hrub{\'a} and A. Popelov{\'a} and M. Bencze and V. Pra{\v z}ienkov{\'a} and S. Gengler and H. Kratochv{\'i}lov{\'a} and M. Haluz{\'i}k and B. {\v Z}elezn{\'a} and J. Kune{\v s} and C. H{\"o}lscher and L. Malet{\'i}nsk{\'a}",

year = "2019",

month = jan,

doi = "10.1016/j.neuropharm.2018.11.002",

language = "English",

volume = "144",

pages = "377--387",

journal = "Neuropharmacology",

issn = "0028-3908",

publisher = "Elsevier Ltd",

}

RIS

TY - JOUR

T1 - Liraglutide and a lipidized analog of prolactin-releasing peptide show neuroprotective effects in a mouse model of β-amyloid pathology

AU - Holubová, M.

AU - Hrubá, L.

AU - Popelová, A.

AU - Bencze, M.

AU - Pražienková, V.

AU - Gengler, S.

AU - Kratochvílová, H.

AU - Haluzík, M.

AU - Železná, B.

AU - Kuneš, J.

AU - Hölscher, C.

AU - Maletínská, L.

PY - 2019/1

Y1 - 2019/1

N2 - 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 palm11-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 palm11-PrRP31 in double transgenic APP/PS1 mice, a model of AD-like β-amyloid (Aβ) pathology. The 7-8-month-old APP/PS1 male mice were subcutaneously injected with liraglutide or palm11-PrRP31 for 2 months. Both the liraglutide and palm11-PrRP31 treatments reduced the Aβ plaque load in the hippocampus. Palm11-PrRP31 also significantly reduced hippocampal microgliosis, consistent with our observations of a reduced Aβ plaque load, and reduced cortical astrocytosis, similar to the treatment with liraglutide. Palm11-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 palm11-PrRP31 reduced the levels of caspase 3, which has multiple roles in the pathogenesis of AD. Palm11-PrRP31 increased protein levels of the pre-synaptic marker synaptophysin, suggesting that palm11-PrRP31 might help preserve synapses. These results indicate that palm11-PrRP31 has promising potential for the treatment of neurodegenerative diseases. © 2018 Elsevier Ltd

AB - 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 palm11-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 palm11-PrRP31 in double transgenic APP/PS1 mice, a model of AD-like β-amyloid (Aβ) pathology. The 7-8-month-old APP/PS1 male mice were subcutaneously injected with liraglutide or palm11-PrRP31 for 2 months. Both the liraglutide and palm11-PrRP31 treatments reduced the Aβ plaque load in the hippocampus. Palm11-PrRP31 also significantly reduced hippocampal microgliosis, consistent with our observations of a reduced Aβ plaque load, and reduced cortical astrocytosis, similar to the treatment with liraglutide. Palm11-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 palm11-PrRP31 reduced the levels of caspase 3, which has multiple roles in the pathogenesis of AD. Palm11-PrRP31 increased protein levels of the pre-synaptic marker synaptophysin, suggesting that palm11-PrRP31 might help preserve synapses. These results indicate that palm11-PrRP31 has promising potential for the treatment of neurodegenerative diseases. © 2018 Elsevier Ltd

KW - Alzheimer's disease

KW - APP/PS1 mice

KW - Neuroinflammation

KW - Palm11-PrRP31

KW - Tau phosphorylation

KW - β-amyloid plaques

U2 - 10.1016/j.neuropharm.2018.11.002

DO - 10.1016/j.neuropharm.2018.11.002

M3 - Journal article

VL - 144

SP - 377

EP - 387

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -

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