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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
A JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Lindemann, L., Jaeschke, G., Michalon, A., Vieira, E., Honer, M., Spooren, W., Porter, R., Hartung, T., Kolczewski, S., Büttelmann, B., et al. (1909) · JAMA · doi:10.1001/jama.1909.02550020033007 · Cited by 7,889
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110
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
West, M. J., Slomianka, L., & Gundersen, H. J. G. (1991) · The Anatomical Record · doi:10.1002/ar.1092310411 · Cited by 2,994
Wu, D. C., Jackson-Lewis, V., Vila, M., Tieu, K., Teismann, P., Vadseth, C., Choi, D.-K., Ischiropoulos, H., & Przedborski, S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-05-01763.2002 · Cited by 1,183
Liberatore, G. T., Jackson-Lewis, V., Vukosavic, S., Mandir, A. S., Vila, M., McAuliffe, W. G., Dawson, V. L., Dawson, T. M., & Przedborski, S. (1999) · Nature Medicine · doi:10.1038/70978 · Cited by 1,046 · cited 4×
“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).”
InfluentialBanati, R. B., Gehrmann, J., Schubert, P., & Kreutzberg, G. W. (1993) · Glia · doi:10.1002/glia.440070117 · Cited by 1,032
MICROGLIA AS MEDIATORS OF INFLAMMATORY AND DEGENERATIVE DISEASES
González-Scarano, F., & Baltuch, G. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.219 · Cited by 984
D'Mello, S. R., Galli, C., Ciotti, T., & Calissano, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.10989 · Cited by 892
Mogi, M., Harada, M., Kondo, T., Riederer, P., Inagaki, H., Minami, M., & Nagatsu, T. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90508-8 · Cited by 855
Glucagon-like peptide-1 receptor is involved in learning and neuroprotection
During, M. J., Cao, L., Zuzga, D. S., Francis, J. S., Fitzsimons, H. L., Jiao, X., Bland, R. J., Klugmann, M., Banks, W. A., Drucker, D. J., et al. (2003) · Nature Medicine · doi:10.1038/nm919 · Cited by 851
Kim, Y. S., & Joh, T. H. (2006) · Experimental & Molecular Medicine · doi:10.1038/emm.2006.40 · Cited by 655
Nitric oxide synthase and neuronal vulnerability in parkinson's disease
Hunot, S., Boissière, F., Faucheux, B., Brugg, B., Mouatt-Prigent, A., Agid, Y., & Hirsch, E. C. (1996) · Neuroscience · doi:10.1016/0306-4522(95)00578-1 · Cited by 595
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
Glucagon-like Peptide-1 Receptor Signaling Modulates β Cell Apoptosis
Li, Y., Hansotia, T., Yusta, B., Ris, F., Halban, P. A., & Drucker, D. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209423200 · Cited by 589
Brubaker, P. L., & Drucker, D. J. (2004) · Endocrinology · doi:10.1210/en.2004-0015 · Cited by 537
Göke, R., Larsen, P. J., Mikkelsen, J. D., & Sheikh, S. P. (1995) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1995.tb00650.x · Cited by 474
Protection and Reversal of Excitotoxic Neuronal Damage by Glucagon-Like Peptide-1 and Exendin-4
Perry, T., Haughey, N. J., Mattson, M. P., Egan, J. M., & Greig, N. H. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.037481 · Cited by 380
Cellular pathology of Parkinson?s disease: astrocytes, microglia and inflammation
Teismann, P., & Schulz, J. B. (2004) · Cell and Tissue Research · doi:10.1007/s00441-004-0944-0 · Cited by 371
Sriram, K., Matheson, J. M., Benkovic, S. A., Miller, D. B., Luster, M. I., & O'Callaghan, J. P. (2002) · The FASEB Journal · doi:10.1096/fj.02-0216fje · Cited by 362
Entry 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
Liu, B., Du, L., & Hong, J.-S. (2000) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39275-4 · Cited by 347 · cited 1×
“In fact, it has been demonstrated that several agents have neuroprotective effects due to their ability to suppress the microglial activation in several PD models (Liu et al. 2000, 2003, Wu et al. 2002, Delgado & Ganea 2003).”
Perry, T., Lahiri, D. K., Sambamurti, K., Chen, D., Mattson, M. P., Egan, J. M., & Greig, N. H. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10611 · Cited by 347
Bertilsson, G., Patrone, C., Zachrisson, O., Andersson, A., Dannaeus, K., Heidrich, J., Kortesmaa, J., Mercer, A., Nielsen, E., Rönnholm, H., et al. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21483 · Cited by 345
Deficiency of Inducible Nitric Oxide Synthase Protects Against MPTP Toxicity In Vivo
Dehmer, T., Lindenau, J. H., Haid, S., DICHGANS, J., & Schulz, J. B. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0742213.x · Cited by 337
Glial cells and inflammation in parkinson's disease: A role in neurodegeneration?
Hirsch, É. C., Hunot, S., Damier, P., & Faucheux, B. A. (1998) · Annals of Neurology · doi:10.1002/ana.410440717 · Cited by 334
Cytokines in Parkinson’s disease
Nagatsu, T., Mogi, M., Ichinose, H., & Togari, A. (2000) · Springer eBooks · doi:10.1007/978-3-7091-6284-2_12 · Cited by 327
The role of glial cells in Parkinsonʼs disease
Vila, M., Jackson-Lewis, V., Guégan, C., Chu Wu, D., Teismann, P., Choi, D.-K., Tieu, K., & Przedborski, S. (2001) · Current Opinion in Neurology · doi:10.1097/00019052-200108000-00009 · Cited by 326
Perry, T., Lahiri, D. K., Chen, D., Zhou, J., Shaw, K. T. Y., Egan, J. M., & Greig, N. H. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.300.3.958 · Cited by 303
Harkavyi, A., Abuirmeileh, A. N., Lever, R., Kingsbury, A. E., Biggs, C. S., & Whitton, P. S. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-19 · Cited by 294
Pathogenic role of glial cells in Parkinson's disease
Teismann, P., Tieu, K., Cohen, O. S., Choi, D., Wu, D. C., Marks, D., Vila, M., Jackson-Lewis, V. R., & Przedborski, S. (2002) · Movement Disorders · doi:10.1002/mds.10332 · Cited by 276
Kim, Y. S., Kim, S. S., Cho, J. J., Choi, D. H., Hwang, O., Shin, D. H., Chun, H. S., Beal, M. F., & Joh, T. H. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4346-04.2005 · Cited by 256
Self-citationCyclic AMP Elevation Is Sufficient to Promote the Survival of Spinal Motor NeuronsIn Vitro
Hanson, M. G., Shen, S., Wiemelt, A. P., McMorris, F. A., & Barres, B. A. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-18-07361.1998 · Cited by 216
Glucagon-like peptide-1 inhibits LPS-induced IL-1β production in cultured rat astrocytes
Iwai, T., Ito, S., Tanimitsu, K., Udagawa, S., & Oka, J.-I. (2006) · Neuroscience Research · doi:10.1016/j.neures.2006.04.008 · Cited by 207
Liu, Y., Qin, L., Li, G., Zhang, W., An, L., Liu, B., & Hong, J. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.043166 · Cited by 205
Kim, Y. S., Choi, D. H., Block, M. L., Lorenzl, S., Yang, L., Kim, Y., Sugama, S., Cho, B. P., Hwang, O., Browne, S. E., et al. (2006) · The FASEB Journal · doi:10.1096/fj.06-5865com · Cited by 199
Self-citationPerry, T., Holloway, H. W., Weerasuriya, A., Mouton, P. R., Duffy, K. B., Mattison, J. A., & Greig, N. H. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.09.028 · Cited by 183
Delgado, M., & Ganea, D. (2003) · The FASEB Journal · doi:10.1096/fj.02-0799fje · Cited by 166
Doyle, M. E. (2001) · Recent Progress in Hormone Research · doi:10.1210/rp.56.1.377 · Cited by 156
Glucagon-like peptide-1: a major regulator of pancreatic beta-cell function
Perfetti, R., & Merkel, P. A. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.1430717 · Cited by 145
Bessler, H., Djaldetti, R., Salman, H., Bergman, M., & Djaldetti, M. (1999) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(99)80079-1 · Cited by 135
Perry, T., & Greig, N. (2005) · Current Alzheimer Research · doi:10.2174/1567205054367892 · Cited by 127
A novel intracellular role of matrix metalloproteinase‐3 during apoptosis of dopaminergic cells
Choi, D. H., Kim, E., Son, H. J., JOH, T. H., Kim, Y. S., Kim, D., Beal, M. F., & Hwang, O. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05399.x · Cited by 124
The glucagon-like peptides: a double-edged therapeutic sword?
Perry, T., & Greig, N. H. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00160-3 · Cited by 114
Parkinson’s Disease: Current and Future Challenges
Langston, J. W. (2002) · NeuroToxicology · doi:10.1016/s0161-813x(02)00098-0 · Cited by 109
Liu, B. (2006) · The AAPS Journal · doi:10.1208/aapsj080369 · Cited by 100
del R�o, M. R., & DeFelipe, J. (1996) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19960603)369:3 · Cited by 97
Kamegai, J., Unterman, T. G., Frohman, L. A., & Kineman, R. D. (1998) · Endocrinology · doi:10.1210/endo.139.8.6136 · Cited by 70
Mena, M. A., Casarejos, M. J., Bonnin, A., Ramos, J. A., & de Yébenes, J. G. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65062612.x · Cited by 55
Cytokines in Parkinson’s Disease
Nagatsu, T., & Mogi, M. (1998) · Advances in behavioral biology · doi:10.1007/978-1-4615-5337-3_58 · Cited by 53
Park, S., Sohn, S., & Kineman, R. D. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1800369 · Cited by 48
Self-citationArt and artifice in the science of histology
RIO‐HORTEGA, P. D. (1993) · Histopathology · doi:10.1111/j.1365-2559.1993.tb00171.x · Cited by 27
Pathogenic role of glial cells in Parkinson's disease
Przedborski, S., & Goldman, J. E. (2003) · Advances in molecular and cell biology · doi:10.1016/s1569-2558(03)31043-4 · Cited by 15
Banati, R. B., & Kreutzberg, G. W. (1992) · Journal of Neuroimmunology · doi:10.1016/0165-5728(92)90227-c · Cited by 10
Cited by
Sorted by citations
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
