The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease
Abstract
Exendin-4 is a naturally occurring more potent and stable analog of glucagon-like peptide-1 (GLP-1) that selectively binds at the GLP-1 receptor. It has been recently demonstrated that GLP-1 receptor stimulation preserves dopaminergic neurons in cellular and rodent models of Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest that activated microglia actively participate in the pathogenesis of PD neurodegeneration. However, the role of microglia in the neuroprotective properties of exendin-4 is still unknown. Here, we show that, in the mouse MPTP PD model, systemic administration of exendin-4 significantly attenuates the loss of substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic fibers. Exendin-4 prevents MPTP-induced microglial activation in the SNpc and striatum, and the expression of matrix metalloproteinase-3. In addition, exendin-4 also suppressed MPTP-induced expression of pro-inflammatory molecules and tumor necrosis factor α and interleukin-1β. Our data indicate that exendin-4 may act as a survival factor for dopaminergic neurons by functioning as a microglia-deactivating factor and suggest that exendin-4 may be a valuable therapeutic agent for neurodegenerative diseases such as PD.
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“Exendin-4 (10 μg/kg) treatment significantly decreased MPTP-induced microglial activation and suppressed MPTP-induced expression of TNF-α and IL-1β [94].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [94]
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Cites
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Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
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Biology of Incretins: GLP-1 and GIP
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“Microglia-derived NO-mediated nitrate stress plays a pivotal role in the pathogenesis of PD, which is supported by the demonstration that MPTP-induced SNpc dopaminergic neuron loss and the production of ventral midbrain nitrotyrosine are attenuated in mice lacking the iNOS gene (Liberatore et al. 1999).”
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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
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
Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease
Yun, S. P., Kam, T.-I., Panicker, N., Kim, S., Oh, Y., Park, J.-S., Kwon, S.-H., Park, Y. J., Karuppagounder, S. S., Park, H., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0051-5 · Cited by 1,123
Self-citationAthauda, 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
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
Metadata
- Authors
- Kim, S., Moon, M., & Park, S.
- Affiliations
- Kyung Hee University (KR)
- Corresponding author
- Park, Seungjoon
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2009-06-29
- Volume
- 202
- Issue
- 3
- Pages
- 431-439
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2164948885
- Cited by
- 263
- References
- 55
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 14 · 2023: 12 · 2022: 21 · 2021: 22 · 2020: 12 · 2019: 18 · 2018: 20 · 2017: 17 · 2016: 22 · 2015: 19 · 2014: 17 · 2013: 17 · 2012: 15
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Korea Science and Engineering Foundation
- Ministry of Education and Human Resources Development
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- exendin-4, Parkinson's disease, dopaminergic neurons, microglial activation, matrix metalloproteinase-3, MPTP-induced neurotoxicity, substantia nigra pars compacta, neuroprotection, GLP-1 receptor, neuroinflammation, TNF-α, IL-1β, nigrostriatal degeneration
- MeSH terms
- Exenatide, Animals, Corpus Striatum, Disease Models, Animal, Dopamine, Gliosis, Hypoglycemic Agents, Male, Mice, Inbred C57BL, Peptides, Substantia Nigra, Venoms, Gene Expression Regulation, Enzymologic, Microglia, Neuroprotective Agents, Inflammation Mediators, Matrix Metalloproteinase 3, Parkinsonian Disorders, Mice, Matrix Metalloproteinase Inhibitors
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