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Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson's disease mouse model

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Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson's disease mouse model. / Zhang, Liping; Zhang, Lingyu; Li, Lin et al.
In: Neuropeptides, Vol. 71, 10.2018, p. 70-80.

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Zhang L, Zhang L, Li L, Hölscher C. Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson's disease mouse model. Neuropeptides. 2018 Oct;71:70-80. Epub 2018 Jul 11. doi: 10.1016/j.npep.2018.07.003

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Zhang, Liping ; Zhang, Lingyu ; Li, Lin et al. / Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson's disease mouse model. In: Neuropeptides. 2018 ; Vol. 71. pp. 70-80.

Bibtex

@article{6c4518b13f8c4896b2309056a85143e1,
title = "Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson's disease mouse model",
abstract = "Parkinson's disease (PD) is the second most common neurodegenerative disease, and there is no recognised therapy to cure it. Recently, it has been shown that treatments to improve insulin resistance in type 2 diabetes (T2DM) may be useful for PD patients. In previous studies, the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide showed good neuroprotective effects in animal models of PD. In addition, the GLP-1 mimetic exendin-4 has shown good protective effects in PD patients in a phase II clinical trial. Here, we report the protective effects of semaglutide (25 nmol/kg ip. once-daily for 7 days), a new long-acting GLP-1 analogue, in the MPTP mouse model of PD. Moreover, we compared the neuroprotective effect of semaglutide with liraglutide given at the same dose. Our work shows that both semaglutide and liraglutide improved 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor impairments. In addition, both GLP-1 analogues rescued the decrease of tyrosine hydroxylase (TH) levels, alleviated the inflammation response, reduced lipid peroxidation, inhibited the apoptosis pathway, and also increased autophagy- related protein expression, to protect dopaminergic neurons in the substantia nigra and striatum. Moreover, the long-acting GLP-1 analogue semaglutide was superior to liraglutide in most parameters measured in this study. Our results demonstrate that the new long- acting GLP-1 analogue semaglutide may be a promising treatment for PD.",
keywords = "Incretin, Insulin, Autophagy, Inflammation, Dopamine, Growth factor",
author = "Liping Zhang and Lingyu Zhang and Lin Li and Christian H{\"o}lscher",
year = "2018",
month = oct,
doi = "10.1016/j.npep.2018.07.003",
language = "English",
volume = "71",
pages = "70--80",
journal = "Neuropeptides",
issn = "0143-4179",
publisher = "Churchill Livingstone",

}

RIS

TY - JOUR

T1 - Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson's disease mouse model

AU - Zhang, Liping

AU - Zhang, Lingyu

AU - Li, Lin

AU - Hölscher, Christian

PY - 2018/10

Y1 - 2018/10

N2 - Parkinson's disease (PD) is the second most common neurodegenerative disease, and there is no recognised therapy to cure it. Recently, it has been shown that treatments to improve insulin resistance in type 2 diabetes (T2DM) may be useful for PD patients. In previous studies, the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide showed good neuroprotective effects in animal models of PD. In addition, the GLP-1 mimetic exendin-4 has shown good protective effects in PD patients in a phase II clinical trial. Here, we report the protective effects of semaglutide (25 nmol/kg ip. once-daily for 7 days), a new long-acting GLP-1 analogue, in the MPTP mouse model of PD. Moreover, we compared the neuroprotective effect of semaglutide with liraglutide given at the same dose. Our work shows that both semaglutide and liraglutide improved 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor impairments. In addition, both GLP-1 analogues rescued the decrease of tyrosine hydroxylase (TH) levels, alleviated the inflammation response, reduced lipid peroxidation, inhibited the apoptosis pathway, and also increased autophagy- related protein expression, to protect dopaminergic neurons in the substantia nigra and striatum. Moreover, the long-acting GLP-1 analogue semaglutide was superior to liraglutide in most parameters measured in this study. Our results demonstrate that the new long- acting GLP-1 analogue semaglutide may be a promising treatment for PD.

AB - Parkinson's disease (PD) is the second most common neurodegenerative disease, and there is no recognised therapy to cure it. Recently, it has been shown that treatments to improve insulin resistance in type 2 diabetes (T2DM) may be useful for PD patients. In previous studies, the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide showed good neuroprotective effects in animal models of PD. In addition, the GLP-1 mimetic exendin-4 has shown good protective effects in PD patients in a phase II clinical trial. Here, we report the protective effects of semaglutide (25 nmol/kg ip. once-daily for 7 days), a new long-acting GLP-1 analogue, in the MPTP mouse model of PD. Moreover, we compared the neuroprotective effect of semaglutide with liraglutide given at the same dose. Our work shows that both semaglutide and liraglutide improved 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor impairments. In addition, both GLP-1 analogues rescued the decrease of tyrosine hydroxylase (TH) levels, alleviated the inflammation response, reduced lipid peroxidation, inhibited the apoptosis pathway, and also increased autophagy- related protein expression, to protect dopaminergic neurons in the substantia nigra and striatum. Moreover, the long-acting GLP-1 analogue semaglutide was superior to liraglutide in most parameters measured in this study. Our results demonstrate that the new long- acting GLP-1 analogue semaglutide may be a promising treatment for PD.

KW - Incretin

KW - Insulin

KW - Autophagy

KW - Inflammation

KW - Dopamine

KW - Growth factor

U2 - 10.1016/j.npep.2018.07.003

DO - 10.1016/j.npep.2018.07.003

M3 - Journal article

VL - 71

SP - 70

EP - 80

JO - Neuropeptides

JF - Neuropeptides

SN - 0143-4179

ER -