Lactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson’s disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis
Abstract Parkinson’s disease (PD) is a debilitating neurological disorder characterized by motor dysfunction, which has been associated with alterations in the gut microbiota. Lactobacillus reuteri (L. reuteri), a safe and versatile probiotic, exhibits potent immunomodulatory functions and neuroprot...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-025-01022-y |
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| author | Xuechao Dong Teng Yang Zheng Jin |
| author_facet | Xuechao Dong Teng Yang Zheng Jin |
| author_sort | Xuechao Dong |
| collection | DOAJ |
| description | Abstract Parkinson’s disease (PD) is a debilitating neurological disorder characterized by motor dysfunction, which has been associated with alterations in the gut microbiota. Lactobacillus reuteri (L. reuteri), a safe and versatile probiotic, exhibits potent immunomodulatory functions and neuroprotective effects. However, the extent and mechanisms by which L. reuteri mitigates PD remain unclear. Here, we demonstrated that L. reuteri significantly alleviated MPTP-induced PD in mice. Importantly, we found that the protective effects of L. reuteri are mediated by its bioactive metabolites rather than the bacteria themselves. Specifically, L. reuteri elevated the levels of γ-aminobutyric acid (GABA). Administration of GABA to mice mitigated MPTP-induced PD. Mechanistically, GABA inhibited MPTP-induced ferroptosis in neuronal cells through activation of the AKT-GSK3β-GPX4 pathway via the GABA receptor. Collectively, our research elucidates that L. reuteri-derived GABA attenuates MPTP-induced PD by inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis, providing a potential therapeutic approach for the prevention and treatment of PD. |
| format | Article |
| id | doaj-art-db83dd91a2be4d41958961567ebe5e1f |
| institution | DOAJ |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-db83dd91a2be4d41958961567ebe5e1f2025-08-20T03:10:38ZengNature Portfolionpj Parkinson's Disease2373-80572025-06-0111111210.1038/s41531-025-01022-yLactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson’s disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axisXuechao Dong0Teng Yang1Zheng Jin2Department of Neurosurgery, The First Hospital of Jilin UniversityDepartment of Orthopedics, The First Hospital of Jilin UniversityDepartment of Neurosurgery, The First Hospital of Jilin UniversityAbstract Parkinson’s disease (PD) is a debilitating neurological disorder characterized by motor dysfunction, which has been associated with alterations in the gut microbiota. Lactobacillus reuteri (L. reuteri), a safe and versatile probiotic, exhibits potent immunomodulatory functions and neuroprotective effects. However, the extent and mechanisms by which L. reuteri mitigates PD remain unclear. Here, we demonstrated that L. reuteri significantly alleviated MPTP-induced PD in mice. Importantly, we found that the protective effects of L. reuteri are mediated by its bioactive metabolites rather than the bacteria themselves. Specifically, L. reuteri elevated the levels of γ-aminobutyric acid (GABA). Administration of GABA to mice mitigated MPTP-induced PD. Mechanistically, GABA inhibited MPTP-induced ferroptosis in neuronal cells through activation of the AKT-GSK3β-GPX4 pathway via the GABA receptor. Collectively, our research elucidates that L. reuteri-derived GABA attenuates MPTP-induced PD by inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis, providing a potential therapeutic approach for the prevention and treatment of PD.https://doi.org/10.1038/s41531-025-01022-y |
| spellingShingle | Xuechao Dong Teng Yang Zheng Jin Lactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson’s disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis npj Parkinson's Disease |
| title | Lactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson’s disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis |
| title_full | Lactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson’s disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis |
| title_fullStr | Lactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson’s disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis |
| title_full_unstemmed | Lactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson’s disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis |
| title_short | Lactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson’s disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis |
| title_sort | lactobacillus reuteri derived γ amino butyric acid alleviates mptp induced parkinson s disease through inhibiting ferroptosis via the akt gsk3β gpx4 axis |
| url | https://doi.org/10.1038/s41531-025-01022-y |
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