Cited by 263Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

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Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease

Kim, Sehee, Moon, Minho, Park, Seungjoon·2009·Journal of Endocrinology

DOI 10.1677/joe-09-0132

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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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Authors: Kim, S., Moon, M., & Park, S.
Affiliations: Kyung Hee University (KR)
Corresponding author: Park, Seungjoon
ORCID: Kim, Sehee
Moon, Minho
Venue: Journal of Endocrinology
Publisher: Bioscientifica
Published: 2009-06-29
Volume: 202
Issue: 3
Pages: 431-439
ISSN: 0022-0795 (ISSN-L)
1479-6805
DOI: 10.1677/joe-09-0132
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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Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease

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