The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease
Open accessAbstract
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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“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]
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“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]
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Cites
Biology of Incretins: GLP-1 and GIP
Baggio, L. L., & Drucker, D. J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.054 · Cited by 3,639
Pharmacology, physiology, and mechanisms of incretin hormone action.
Campbell, J. E., & Drucker, D. J. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.008 · Cited by 1,500
McClean, P. L., Parthsarathy, V., Faivre, E., & Hölscher, C. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0529-11.2011 · Cited by 698
Self-citationIncretin-based therapies for type 2 diabetes mellitus
Lovshin, J. A., & Drucker, D. J. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.48 · Cited by 645
Li, Y., Perry, T., Kindy, M. S., Harvey, B. K., Tweedie, D., Holloway, H. W., Powers, K., Shen, H., Egan, J. M., Sambamurti, K., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806720106 · Cited by 589
Exenatide and the treatment of patients with Parkinson's disease
Aviles-Olmos, I., Dickson, J., Kefalopoulou, Z., Djamshidian, A., Ell, P., Soderlund, T., Whitton, P., Wyse, R., Isaacs, T., Lees, A., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68295 · Cited by 529
Hunter, K., & Hölscher, C. (2012) · BMC Neuroscience · doi:10.1186/1471-2202-13-33 · Cited by 504
Self-citationInteractions of Glucagon-Like Peptide-1 (GLP-1) with the Blood-Brain Barrier
Kastin, A. J., Akerstrom, V., & Pan, W. (2002) · Journal of Molecular Neuroscience · doi:10.1385/jmn:18:1-2:07 · Cited by 480
McClean, P. L., & Hölscher, C. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.08.005 · Cited by 362
Self-citationEntry of exendin-4 into brain is rapid but may be limited at high doses
Kastin, A. J., & Akerstrom, V. L. (2003) · International Journal of Obesity · doi:10.1038/sj.ijo.0802206 · Cited by 358
Cited by
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Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868
Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States
Mattson, M. P., & Arumugam, T. V. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.05.011 · Cited by 1,242
Glucagon-like peptide-1 receptor: mechanisms and advances in therapy
Zheng, Z., Zong, Y., Ma, Y., Tian, Y., Pang, Y., Zhang, C., & Gao, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01931-z · Cited by 1,036
Athauda, D., Maclagan, K., Skene, S. S., Bajwa-Joseph, M., Letchford, D., Chowdhury, K., Hibbert, S., Budnik, N., Zampedri, L., Dickson, J., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31585-4 · Cited by 889
The Role of Autophagy in Parkinson's DiseasePreprint
Lynch-Day, M. A., Mao, K., Wang, K., Zhao, M., & Klionsky, D. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009357 · Cited by 477
Metadata
- 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
- 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 › 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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