Compensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout mice
Abstract Animal models are crucial for elucidating the pathological mechanisms underlying Parkinson’s disease (PD). Unfortunately, most of transgenic mouse models fail to manifest pathological changes observed in PD patients, pending the advancement of PD research. However, the mechanism underlying...
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BMC
2025-02-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02037-x |
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| author | Nan Dong Zhenli Xie Anqi Wei Yuxin Yang Yongning Deng Xu Cheng Bianbian Wang Yang Chen Yuhao Gu Jingyu Yao Yuhao Qin Chaowen Zheng Xi Zhang Yuqing Zhang Xinjiang Kang Guoqing Chen Qiumin Qu Changhe Wang Huadong Xu |
| author_facet | Nan Dong Zhenli Xie Anqi Wei Yuxin Yang Yongning Deng Xu Cheng Bianbian Wang Yang Chen Yuhao Gu Jingyu Yao Yuhao Qin Chaowen Zheng Xi Zhang Yuqing Zhang Xinjiang Kang Guoqing Chen Qiumin Qu Changhe Wang Huadong Xu |
| author_sort | Nan Dong |
| collection | DOAJ |
| description | Abstract Animal models are crucial for elucidating the pathological mechanisms underlying Parkinson’s disease (PD). Unfortunately, most of transgenic mouse models fail to manifest pathological changes observed in PD patients, pending the advancement of PD research. However, the mechanism underlying this discrepancy remains elusive. Here, we provide compelling evidence that the compensatory expression of synaptotagmin-11 (Syt11) plays a key role in concealing PD-associated phenotypes in parkin knockout (KO) mouse models. Unlike the normal dopamine (DA) release and motor behaviors observed in parkin KO mice, parkin knockdown (KD) in the substantia nigra pars compacta (SNpc) in adult mice led to both the impaired DA release and the pronounced motor deficits. Interestingly, Syt11, a well-established parkin substrate involved in PD, was specifically upregulated in parkin KD mice and in parkin KO mice during the suckling stage, but not in adult parkin KO mice. Importantly, the overexpression of Syt11 alone is capable of inducing PD-like motor and non-motor impairments, as well as the impaired DA release and reuptake, which is essential for parkin-associated pathogenesis of PD. Therefore, this work not only elucidate a compensatory mechanism that accounts for the absence of overt PD phenotypes in parkin KO mice, but also contribute to the comprehensive understanding of the progression of PD, opening new avenues for the therapeutic treatment of PD. |
| format | Article |
| id | doaj-art-de50e58a7eda4335b06a7f89dac7e68d |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-de50e58a7eda4335b06a7f89dac7e68d2025-02-09T12:47:27ZengBMCCell Communication and Signaling1478-811X2025-02-0123111210.1186/s12964-025-02037-xCompensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout miceNan Dong0Zhenli Xie1Anqi Wei2Yuxin Yang3Yongning Deng4Xu Cheng5Bianbian Wang6Yang Chen7Yuhao Gu8Jingyu Yao9Yuhao Qin10Chaowen Zheng11Xi Zhang12Yuqing Zhang13Xinjiang Kang14Guoqing Chen15Qiumin Qu16Changhe Wang17Huadong Xu18Department of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong UniversityDepartment of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong UniversityDepartment of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong UniversityCollege of Life Sciences, Liaocheng UniversityDepartment of Neurology, the First Affiliated Hospital of Xi’an Jiaotong UniversityKey Laboratory of Medical Electrophysiology, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Ministry of Education of China, Southwest Medical UniversityDepartment of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong UniversityDepartment of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong UniversityDepartment of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong UniversityDepartment of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Medical Electrophysiology, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Ministry of Education of China, Southwest Medical UniversityDepartment of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong UniversityXuanwu Hospital, Capital Medical UniversityXuanwu Hospital, Capital Medical UniversityKey Laboratory of Medical Electrophysiology, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Ministry of Education of China, Southwest Medical UniversityState Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, Tsinghua Center for Life Sciences, PKU-IDG/ McGovern Institute for Brain Research, Peking UniversityDepartment of Neurology, the First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong UniversityDepartment of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong UniversityAbstract Animal models are crucial for elucidating the pathological mechanisms underlying Parkinson’s disease (PD). Unfortunately, most of transgenic mouse models fail to manifest pathological changes observed in PD patients, pending the advancement of PD research. However, the mechanism underlying this discrepancy remains elusive. Here, we provide compelling evidence that the compensatory expression of synaptotagmin-11 (Syt11) plays a key role in concealing PD-associated phenotypes in parkin knockout (KO) mouse models. Unlike the normal dopamine (DA) release and motor behaviors observed in parkin KO mice, parkin knockdown (KD) in the substantia nigra pars compacta (SNpc) in adult mice led to both the impaired DA release and the pronounced motor deficits. Interestingly, Syt11, a well-established parkin substrate involved in PD, was specifically upregulated in parkin KD mice and in parkin KO mice during the suckling stage, but not in adult parkin KO mice. Importantly, the overexpression of Syt11 alone is capable of inducing PD-like motor and non-motor impairments, as well as the impaired DA release and reuptake, which is essential for parkin-associated pathogenesis of PD. Therefore, this work not only elucidate a compensatory mechanism that accounts for the absence of overt PD phenotypes in parkin KO mice, but also contribute to the comprehensive understanding of the progression of PD, opening new avenues for the therapeutic treatment of PD.https://doi.org/10.1186/s12964-025-02037-xParkinson’s diseaseCompensatory effectParkinSynaptotagmin-11Dopamine release |
| spellingShingle | Nan Dong Zhenli Xie Anqi Wei Yuxin Yang Yongning Deng Xu Cheng Bianbian Wang Yang Chen Yuhao Gu Jingyu Yao Yuhao Qin Chaowen Zheng Xi Zhang Yuqing Zhang Xinjiang Kang Guoqing Chen Qiumin Qu Changhe Wang Huadong Xu Compensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout mice Cell Communication and Signaling Parkinson’s disease Compensatory effect Parkin Synaptotagmin-11 Dopamine release |
| title | Compensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout mice |
| title_full | Compensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout mice |
| title_fullStr | Compensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout mice |
| title_full_unstemmed | Compensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout mice |
| title_short | Compensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout mice |
| title_sort | compensatory synaptotagmin 11 expression conceals parkinson s disease like phenotypes in parkin knockout mice |
| topic | Parkinson’s disease Compensatory effect Parkin Synaptotagmin-11 Dopamine release |
| url | https://doi.org/10.1186/s12964-025-02037-x |
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