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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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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Earlier GLP-1RAs, such as liraglutide and lixisenatide, have been shown to protect dopaminergic neurons and reduce motor disability in animal models.
“Regarding Parkinson disease, earlier GLP-1RAs, such as liraglutide and lixisenatide, have been shown to protect dopaminergic neurons and reduce motor disability in animal models.32”
From Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity (2025) · cites this paper as [32]
GLP-1RAs exhibit noticeable increase in level of phosphorylated ERK1/2 within sciatic nerve of diabetic rats.
“Researchers have discovered that GLP-1RAs exhibit a noticeable increase in the level of phosphorylated ERK1/2 within the sciatic nerve of diabetic rats.”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [401]
The Discussion mentions GLP-1 receptor signaling through MAPk2 and PKA, but does not report phosphorylated ERK1/2 levels in sciatic nerves. The reported experiments concern an MPTP mouse model of Parkinson’s disease, not diabetic rats. Searches for phosphorylated ERK1/2 and sciatic nerve findings found no passage addressing the claimed result. (LLM, conf=0.76)
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Self-citation
- Authors
- Liu, W., Jalewa, J., Sharma, M., Li, G., Li, L., & Hölscher, C.
- Affiliations
- Shanxi Medical University (CN)
- Lancaster University (GB)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 303
- Pages
- 42-50
- ISSN
- 0306-4522 (ISSN-L)
- 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 · 2012: 1
- FWCI
- 14.33
- Type
- journal article
- Language
- en
- Open access
- green
- eprints.lancs.ac.uk
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Lancaster EPrints (Lancaster University) (submittedVersion)
- Funders
- Cure Parkinson’s Trust, UK
- Shanxi Province Government, China
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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