Cited by 246Parkinson's Disease Mechanisms and TreatmentsAlzheimer's disease research and treatmentsNuclear Receptors and Signaling

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Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease

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Liu, W., Jalewa, J., Sharma, M., Li, G., Li, L., Hölscher, C.·2015·Neuroscience

DOI 10.1016/j.neuroscience.2015.06.054

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Abstract

Glucagon-like peptide 1 (GLP-1) is a growth factor. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. These drugs have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a clinical trial in PD patients showed promising first results. Liraglutide and lixisenatide are two newer GLP-1 mimetics which have a longer biological half-life than exendin-4. We previously showed that these drugs have neuroprotective properties in an animal model of Alzheimer's disease. Here we demonstrate the neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20mg/kg i.p.) for 7 days, and drugs were injected once-daily for 14 days i.p. When comparing exendin-4 (10 nmol/kg), liraglutide (25 nmol/kg) and lixisenatide (10 nmol/kg), it was found that exendin-4 showed no protective effects at the dose chosen. Both liraglutide and lixisenatide showed effects in preventing the MPTP-induced motor impairment (Rotarod, open-field locomotion, catalepsy test), reduction in tyrosine hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, a reduction of the pro-apoptotic signaling molecule BAX and an increase in the anti-apoptotic signaling molecule B-cell lymphoma-2. The results demonstrate that in this study, both liraglutide and lixisenatide are superior to exendin-4, and both drugs show promise as a novel treatment of PD.

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Authors: Liu, W., Jalewa, J., Sharma, M., Li, G., Li, L., & Hölscher, C.
Affiliations: Shanxi Medical University (CN)
Lancaster University (GB)
ORCID: Jalewa, J.
Sharma, M.
Hölscher, C.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2015-09
Volume: 303
Pages: 42-50
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2015.06.054
OpenAlex: W2211963426
Cited by: 246
References: 38
Citations by year: 2026: 24 · 2025: 27 · 2024: 32 · 2023: 15 · 2022: 33 · 2021: 20 · 2020: 16 · 2019: 17 · 2018: 27 · 2017: 11 · 2016: 16 · 2015: 7
FWCI: 14.33
Type: journal article
Language: en
Open access: green
eprints.lancs.ac.uk
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Lancaster EPrints (Lancaster University) (submittedVersion)
Funders: Cure Parkinson’s Trust, UK
Shanxi Province Government, China
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: Parkinson's disease, liraglutide, lixisenatide, GLP-1 receptor agonists, neuroprotection, MPTP mouse model, exendin-4, dopamine synthesis, substantia nigra, Bax, Bcl-2, apoptosis, motor impairment, catalepsy
MeSH terms: Glucagon-Like Peptide-2 Receptor, Liraglutide, Exenatide, Animals, Basal Ganglia, Catalepsy, Disease Models, Animal, Male, Mice, Inbred C57BL, Motor Activity, Peptides, Substantia Nigra, Tyrosine 3-Monooxygenase, Venoms, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Apoptosis, Neuroprotective Agents, Parkinsonian Disorders, Rotarod Performance Test, Mice, Dopaminergic Neurons

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Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease

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