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GIP has neuroprotective effects in Alzheimer and Parkinson’s disease models

•GIP is a hormone and a growth factor that plays key roles in the brain.•Protease-resistant GIP analogues show neuroprotective effects in animal models.•Cognition and synaptic plasticity is protected in animal models of Alzheimer’s disease.•Neuronal energy utilisation, cell repair and mitochondrial...

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Published in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2020-03, Vol.125, p.170184-170184, Article 170184
Main Authors: Zhang, Zhen Qiang, Hölscher, Christian
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Language:English
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description •GIP is a hormone and a growth factor that plays key roles in the brain.•Protease-resistant GIP analogues show neuroprotective effects in animal models.•Cognition and synaptic plasticity is protected in animal models of Alzheimer’s disease.•Neuronal energy utilisation, cell repair and mitochondrial function is protected.•Motor activity and dopaminergic neuronal function is protected in models of Parkinson’s disease. Glucose-dependent Insulinotropic polypeptide (GIP) is a peptide hormone of the incretin family. It has growth factor properties and can re-activate energy utilization. In progressive neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, energy utilization is much reduced, and GIP has the potential to reverse this. Furthermore, GIP can reduce the inflammation response in the brain and reduce levels of pro-inflammatory cytokines. Tests in animal models of Alzheimer’s and Parkinson’s disease show good neuroprotective effects. In Parkinson’s disease models, motor activity is normalized, dopaminergic neurons are protected, synapse numbers and dopamine levels are maintained. Levels of growth factors that are essential for neuronal and synaptic function are increased and alpha-synuclein levels are reduced. The chronic inflammation response and mitochondrial damage is reduced. In Alzheimer’s disease models, memory is rescued, synapse numbers and synaptic plasticity in the hippocampus is normalized, amyloid plaque load and the chronic inflammation is reduced. Similar protective effects have been previously reported with analogues of glucagon-like peptide 1 (GLP-1), the sister incretin hormone. First clinical trials show good protective effects in both diseases. Recently, novel dual GLP-1/GIP receptor agonists have been developed. The ability to cross the blood-brain barrier (BBB) is key to their neuroprotective effects. We have developed two dual GLP-1/GIP receptor agonist that have cell penetrating sequences added for better BBB penetration. In direct comparisons, these dual agonists show improved neuroprotection in a mouse model of Parkinson’s disease. Therefore, such novel multiple receptor agonists hold great promise as potential treatments for Alzheimer’s and Parkinson’s disease.
doi_str_mv 10.1016/j.peptides.2019.170184
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Glucose-dependent Insulinotropic polypeptide (GIP) is a peptide hormone of the incretin family. It has growth factor properties and can re-activate energy utilization. In progressive neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, energy utilization is much reduced, and GIP has the potential to reverse this. Furthermore, GIP can reduce the inflammation response in the brain and reduce levels of pro-inflammatory cytokines. Tests in animal models of Alzheimer’s and Parkinson’s disease show good neuroprotective effects. In Parkinson’s disease models, motor activity is normalized, dopaminergic neurons are protected, synapse numbers and dopamine levels are maintained. Levels of growth factors that are essential for neuronal and synaptic function are increased and alpha-synuclein levels are reduced. The chronic inflammation response and mitochondrial damage is reduced. In Alzheimer’s disease models, memory is rescued, synapse numbers and synaptic plasticity in the hippocampus is normalized, amyloid plaque load and the chronic inflammation is reduced. Similar protective effects have been previously reported with analogues of glucagon-like peptide 1 (GLP-1), the sister incretin hormone. First clinical trials show good protective effects in both diseases. Recently, novel dual GLP-1/GIP receptor agonists have been developed. The ability to cross the blood-brain barrier (BBB) is key to their neuroprotective effects. We have developed two dual GLP-1/GIP receptor agonist that have cell penetrating sequences added for better BBB penetration. In direct comparisons, these dual agonists show improved neuroprotection in a mouse model of Parkinson’s disease. 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In Alzheimer’s disease models, memory is rescued, synapse numbers and synaptic plasticity in the hippocampus is normalized, amyloid plaque load and the chronic inflammation is reduced. Similar protective effects have been previously reported with analogues of glucagon-like peptide 1 (GLP-1), the sister incretin hormone. First clinical trials show good protective effects in both diseases. Recently, novel dual GLP-1/GIP receptor agonists have been developed. The ability to cross the blood-brain barrier (BBB) is key to their neuroprotective effects. We have developed two dual GLP-1/GIP receptor agonist that have cell penetrating sequences added for better BBB penetration. In direct comparisons, these dual agonists show improved neuroprotection in a mouse model of Parkinson’s disease. 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ispartof Peptides (New York, N.Y. : 1980), 2020-03, Vol.125, p.170184-170184, Article 170184
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subjects Alzheimer Disease - pathology
Alzheimer Disease - prevention & control
Animals
Brain
Disease Models, Animal
Gastric Inhibitory Polypeptide - pharmacology
Gastrointestinal Agents - pharmacology
GLP-1
Growth factor
Humans
Incretins
Insulin
Mice
Mitochondria
Neurodegeneration
Neuroprotective Agents - pharmacology
Parkinson Disease - pathology
Parkinson Disease - prevention & control
title GIP has neuroprotective effects in Alzheimer and Parkinson’s disease models
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