Neurotrophic Role of the Next-Generation Probiotic Strain L. lactis MG1363-pMG36e-GLP-1 on Parkinson’s Disease via Inhibiting Ferroptosis
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Parkinson’s disease (PD) is a neurodegenerative disease (NDD) with high and ongoing morbidity, bringing heavy burdens to PD patients seriously. Finding neurotrophic drugs still remains vital due to the limited drug spectrum available currently. Substantial evidence suggests that glucagon-like peptide 1 (GLP-1) exerts neuroprotection on PD, yet the short-lived biological activity markedly hindered its application. Herein, we investigated the neurotrophic role of the next-generation probiotic strain L. lactis MG1363-pMG36e-GLP-1 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and elucidated the mechanisms. Our data suggested that L. lactis MG1363-pMG36e-GLP-1 markedly enhanced motor deficits induced by MPTP via rescuing dopaminergic (DAergic) neurodegeneration in substantia nigra (SN). We found that L. lactis MG1363-pMG36e-GLP-1 exerts neurotrophic effects via activating the Keap1/Nrf2/GPX4 signalling pathway to down-regulate ACSL4 and up-regulate FSP1 to suppress ferroptosis. Additionally, the decreased oxidative stress levels via suppressing generations of ROS and MDA supported our findings. Lastly, we identified that the L. lactis MG1363-pMG36e-GLP-1 administration reversed dysbiosis in PD mice by increasing Akkermansia, Oscillospira, and Sutterella at the genus level. These results indicated that the neurotrophic effects of the next-generation probiotics L. lactis MG1363-pMG36e-GLP-1 against MPTP-induced Parkinsonism are mediated by modulating oxidative stress, inhibiting ferroptosis, and redressing dysbiosis.
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An engineered GLP-1-producing probiotic strain, Lactococcus lactis MG1363-pMG36e-GLP-1, counteracts MPTP-induced neurodegeneration by inhibiting glial activation, oxidative stress, and ferroptosis.
“An engineered GLP-1-producing probiotic strain, Lactococcus lactis MG1363-pMG36e-GLP-1, counteracts MPTP-induced neurodegeneration by inhibiting glial activation, oxidative stress, and ferroptosis.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [617]
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- Authors
- Yue, M., Wei, J., Chen, W., Hong, D., Chen, T., & Fang, X.
- Affiliations
- First Affiliated Hospital of Nanchang University (CN)
- Nanchang University (CN)
- Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
- Corresponding author
- Chen, Tingtao
- Fang, Xin
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2022-11-18
- Volume
- 14
- Issue
- 22
- Pages
- 4886
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC9698534
- OpenAlex
- W4309736718
- Cited by
- 62
- References
- 51
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 23 · 2023: 9
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82060638, 82060222, 20213BCJL22049, 202210390)
- Major Disciplines of Academic and Technical Leaders Project of Jiangxi Province (82060638, 82060222, 20213BCJL22049, 202210390)
- Science and Technology Plan of Jiangxi Health Planning Committee (82060638, 82060222, 20213BCJL22049, 202210390)
- Double Thousand Plan of Jiangxi Province (82060638, 82060222, 20213BCJL22049, 202210390)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, probiotics, Lactococcus lactis, glucagon-like peptide-1, ferroptosis, dopaminergic neuron loss, substantia nigra, MPTP-induced neurotoxicity, oxidative stress, gut dysbiosis, Akkermansia, Sutterella, Oscillospira, neuroprotection
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Ferroptosis, Animals, Parkinson Disease, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Neurodegenerative Diseases, Probiotics, NF-E2-Related Factor 2, Mice, Glucagon-Like Peptide 1, Dysbiosis
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