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  • GIP_analogue_in_PD_Neuropharmacol

    Rights statement: This is the author’s version of a work that was accepted for publication in Neuropharmacology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuropharmacology, 101, 2016 DOI: 10.1016/j.neuropharm.2015.10.002

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Neuroprotective effects of a GIP analogue in the MPTP Parkinson's disease mouse model

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Neuroprotective effects of a GIP analogue in the MPTP Parkinson's disease mouse model. / Li, Yanwei; Liu, WeiZhen; Li, Lin et al.
In: Neuropharmacology, Vol. 101, 02.2016, p. 255-263.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

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Li Y, Liu W, Li L, Holscher C. Neuroprotective effects of a GIP analogue in the MPTP Parkinson's disease mouse model. Neuropharmacology. 2016 Feb;101:255-263. Epub 2015 Nov 10. doi: 10.1016/j.neuropharm.2015.10.002

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Li, Yanwei ; Liu, WeiZhen ; Li, Lin et al. / Neuroprotective effects of a GIP analogue in the MPTP Parkinson's disease mouse model. In: Neuropharmacology. 2016 ; Vol. 101. pp. 255-263.

Bibtex

@article{97ba1db3dcee448eaec526bb748f77a2,
title = "Neuroprotective effects of a GIP analogue in the MPTP Parkinson's disease mouse model",
abstract = "Parkinson's disease (PD) is a chronic neurodegenerative disease, and there is no cure for it at present. Recent research has indicated a link between type 2 diabetes mellitus (T2DM) and PD, which suggested that a treatment to improve insulin resistance for T2DM may be useful for PD patients. Glucose-dependent insulinotropic polypeptide (GIP) belongs to the incretin hormone family, which can promote insulin release and improve insulin resistance. Several GIP analogues have been developed as potential treatments for T2DM. In the present study, a novel long-lasting GIP analogue, D-Ala2-GIP-glu-PAL, has been tested in an acute PD mouse model induced by four 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneal injections. D-Ala2-GIP-glu-PAL treatment (25 nmol/kg ip.) for 7 days after MPTP treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement balance of mice. D-Ala2-GIP-glu-PAL treatment also restored tyrosine hydroxylase (TH) positive dopaminergic neuron numbers in the substantia nigra and TH levels in the striatum. D-Ala2-GIP-glu-PAL also reduced the chronic inflammation response as seen in astrocyte and microglia activation in the substantia nigra pars compacta (SNpc). D-Ala2-GIP-glu-PAL reversed the reduction of synapse numbers (synaptophysin levels), decreased the ratio of growth factor and apoptosis signaling molecules Bax/Bcl-2, and improved the decrease of p-CREBS133 growth factor signaling in the substantia nigra. Therefore, D-Ala2-GIP-glu-PAL promotes cell survival of dopaminergic neuron in the SNpc by activating the cAMP/PKA/CREB growth factor second messenger pathway that also inhibits apoptosis. The present results demonstrate that D-Ala2-GIP-glu-PAL shows promise as a novel treatment of PD.",
keywords = "Growth factors, Diabetes, Glucose-dependent insulinotropic polypeptide, Neuroinflammation, Apoptosis, Neuroprotection, Insulin",
author = "Yanwei Li and WeiZhen Liu and Lin Li and Christian Holscher",
note = "This is the author{\textquoteright}s version of a work that was accepted for publication in Neuropharmacology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuropharmacology, 101, 2016 DOI: 10.1016/j.neuropharm.2015.10.002",
year = "2016",
month = feb,
doi = "10.1016/j.neuropharm.2015.10.002",
language = "English",
volume = "101",
pages = "255--263",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Ltd",

}

RIS

TY - JOUR

T1 - Neuroprotective effects of a GIP analogue in the MPTP Parkinson's disease mouse model

AU - Li, Yanwei

AU - Liu, WeiZhen

AU - Li, Lin

AU - Holscher, Christian

N1 - This is the author’s version of a work that was accepted for publication in Neuropharmacology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuropharmacology, 101, 2016 DOI: 10.1016/j.neuropharm.2015.10.002

PY - 2016/2

Y1 - 2016/2

N2 - Parkinson's disease (PD) is a chronic neurodegenerative disease, and there is no cure for it at present. Recent research has indicated a link between type 2 diabetes mellitus (T2DM) and PD, which suggested that a treatment to improve insulin resistance for T2DM may be useful for PD patients. Glucose-dependent insulinotropic polypeptide (GIP) belongs to the incretin hormone family, which can promote insulin release and improve insulin resistance. Several GIP analogues have been developed as potential treatments for T2DM. In the present study, a novel long-lasting GIP analogue, D-Ala2-GIP-glu-PAL, has been tested in an acute PD mouse model induced by four 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneal injections. D-Ala2-GIP-glu-PAL treatment (25 nmol/kg ip.) for 7 days after MPTP treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement balance of mice. D-Ala2-GIP-glu-PAL treatment also restored tyrosine hydroxylase (TH) positive dopaminergic neuron numbers in the substantia nigra and TH levels in the striatum. D-Ala2-GIP-glu-PAL also reduced the chronic inflammation response as seen in astrocyte and microglia activation in the substantia nigra pars compacta (SNpc). D-Ala2-GIP-glu-PAL reversed the reduction of synapse numbers (synaptophysin levels), decreased the ratio of growth factor and apoptosis signaling molecules Bax/Bcl-2, and improved the decrease of p-CREBS133 growth factor signaling in the substantia nigra. Therefore, D-Ala2-GIP-glu-PAL promotes cell survival of dopaminergic neuron in the SNpc by activating the cAMP/PKA/CREB growth factor second messenger pathway that also inhibits apoptosis. The present results demonstrate that D-Ala2-GIP-glu-PAL shows promise as a novel treatment of PD.

AB - Parkinson's disease (PD) is a chronic neurodegenerative disease, and there is no cure for it at present. Recent research has indicated a link between type 2 diabetes mellitus (T2DM) and PD, which suggested that a treatment to improve insulin resistance for T2DM may be useful for PD patients. Glucose-dependent insulinotropic polypeptide (GIP) belongs to the incretin hormone family, which can promote insulin release and improve insulin resistance. Several GIP analogues have been developed as potential treatments for T2DM. In the present study, a novel long-lasting GIP analogue, D-Ala2-GIP-glu-PAL, has been tested in an acute PD mouse model induced by four 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneal injections. D-Ala2-GIP-glu-PAL treatment (25 nmol/kg ip.) for 7 days after MPTP treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement balance of mice. D-Ala2-GIP-glu-PAL treatment also restored tyrosine hydroxylase (TH) positive dopaminergic neuron numbers in the substantia nigra and TH levels in the striatum. D-Ala2-GIP-glu-PAL also reduced the chronic inflammation response as seen in astrocyte and microglia activation in the substantia nigra pars compacta (SNpc). D-Ala2-GIP-glu-PAL reversed the reduction of synapse numbers (synaptophysin levels), decreased the ratio of growth factor and apoptosis signaling molecules Bax/Bcl-2, and improved the decrease of p-CREBS133 growth factor signaling in the substantia nigra. Therefore, D-Ala2-GIP-glu-PAL promotes cell survival of dopaminergic neuron in the SNpc by activating the cAMP/PKA/CREB growth factor second messenger pathway that also inhibits apoptosis. The present results demonstrate that D-Ala2-GIP-glu-PAL shows promise as a novel treatment of PD.

KW - Growth factors

KW - Diabetes

KW - Glucose-dependent insulinotropic polypeptide

KW - Neuroinflammation

KW - Apoptosis

KW - Neuroprotection

KW - Insulin

U2 - 10.1016/j.neuropharm.2015.10.002

DO - 10.1016/j.neuropharm.2015.10.002

M3 - Journal article

VL - 101

SP - 255

EP - 263

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -