The deficiency of Maged1 attenuates Parkinson's disease progression in mice
Abstract Melanoma-associated antigen D1 (Maged1) has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, and drug addiction. However, the role of Maged1 in Parkinson’s disease (PD) remains...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Molecular Brain |
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| Online Access: | https://doi.org/10.1186/s13041-023-01011-3 |
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| author | Jie Wang Sheng-Ye Xu Zhi-Yuan Ye Zhou-Na Sun Jia-Qi Zhang Cui Qi Rui Liu Xiang Gao Chuan He Wei-Yan You Jun Gao |
| author_facet | Jie Wang Sheng-Ye Xu Zhi-Yuan Ye Zhou-Na Sun Jia-Qi Zhang Cui Qi Rui Liu Xiang Gao Chuan He Wei-Yan You Jun Gao |
| author_sort | Jie Wang |
| collection | DOAJ |
| description | Abstract Melanoma-associated antigen D1 (Maged1) has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, and drug addiction. However, the role of Maged1 in Parkinson’s disease (PD) remains unclear. In this study, we observed that Maged1 was expressed in the dopaminergic (DA) neurons of the substantia nigra in mice and humans, which could be upregulated by the in vivo or in vitro treatment with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-Methyl-4-phenylpyridinium iodide (MPP+). Genetic ablation of Maged1 in mice attenuated motor deficits, the loss of DA neurons, and disease progression induced by MPTP. Moreover, Maged1 deficiency protected DA neurons against MPP+-induced toxicity in primary cultured cells. Mechanistically, loss of Maged1 upregulated the Akt signaling pathway and downregulated the mTOR signaling pathway in SH-SY5Y cells, which may in turn attenuate the cell apoptosis and impairment of autophagy. Consistent with it, the degeneration of midbrain and striatum among elderly Maged1 knockout mice was relatively mild compared to those in wild-type mice under physiological conditions. Taken together, this study suggested that Maged1 deficiency inhibited apoptosis and enhanced autophagy, which may provide a new potential target for the therapy of PD. |
| first_indexed | 2024-03-07T14:33:41Z |
| format | Article |
| id | doaj.art-205baf85e9ec4ffe9ef9ee99115adfdb |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-03-07T14:33:41Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-205baf85e9ec4ffe9ef9ee99115adfdb2024-03-05T20:44:36ZengBMCMolecular Brain1756-66062023-02-0116111610.1186/s13041-023-01011-3The deficiency of Maged1 attenuates Parkinson's disease progression in miceJie Wang0Sheng-Ye Xu1Zhi-Yuan Ye2Zhou-Na Sun3Jia-Qi Zhang4Cui Qi5Rui Liu6Xiang Gao7Chuan He8Wei-Yan You9Jun Gao10Department of Neurobiology, School of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Nanjing Medical UniversitySKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing UniversityDepartment of Rehabilitation Medicine, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Nanjing Medical UniversityAbstract Melanoma-associated antigen D1 (Maged1) has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, and drug addiction. However, the role of Maged1 in Parkinson’s disease (PD) remains unclear. In this study, we observed that Maged1 was expressed in the dopaminergic (DA) neurons of the substantia nigra in mice and humans, which could be upregulated by the in vivo or in vitro treatment with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-Methyl-4-phenylpyridinium iodide (MPP+). Genetic ablation of Maged1 in mice attenuated motor deficits, the loss of DA neurons, and disease progression induced by MPTP. Moreover, Maged1 deficiency protected DA neurons against MPP+-induced toxicity in primary cultured cells. Mechanistically, loss of Maged1 upregulated the Akt signaling pathway and downregulated the mTOR signaling pathway in SH-SY5Y cells, which may in turn attenuate the cell apoptosis and impairment of autophagy. Consistent with it, the degeneration of midbrain and striatum among elderly Maged1 knockout mice was relatively mild compared to those in wild-type mice under physiological conditions. Taken together, this study suggested that Maged1 deficiency inhibited apoptosis and enhanced autophagy, which may provide a new potential target for the therapy of PD.https://doi.org/10.1186/s13041-023-01011-3Melanoma-associated antigen D1Parkinson’s diseaseApoptosisAutophagySubstantia nigra |
| spellingShingle | Jie Wang Sheng-Ye Xu Zhi-Yuan Ye Zhou-Na Sun Jia-Qi Zhang Cui Qi Rui Liu Xiang Gao Chuan He Wei-Yan You Jun Gao The deficiency of Maged1 attenuates Parkinson's disease progression in mice Molecular Brain Melanoma-associated antigen D1 Parkinson’s disease Apoptosis Autophagy Substantia nigra |
| title | The deficiency of Maged1 attenuates Parkinson's disease progression in mice |
| title_full | The deficiency of Maged1 attenuates Parkinson's disease progression in mice |
| title_fullStr | The deficiency of Maged1 attenuates Parkinson's disease progression in mice |
| title_full_unstemmed | The deficiency of Maged1 attenuates Parkinson's disease progression in mice |
| title_short | The deficiency of Maged1 attenuates Parkinson's disease progression in mice |
| title_sort | deficiency of maged1 attenuates parkinson s disease progression in mice |
| topic | Melanoma-associated antigen D1 Parkinson’s disease Apoptosis Autophagy Substantia nigra |
| url | https://doi.org/10.1186/s13041-023-01011-3 |
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