The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for Treatment
Alzheimer’s disease (AD), a serious neurodegenerative disease, is pathologically characterized by synaptic loss and dysfunction. Synaptic vesicle protein 2A (SV2A) is an indispensable vesicular protein specifically expressed in synapses and can be used as a biomarker for synaptic density. We found t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.609908/full |
| _version_ | 1818576151371579392 |
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| author | Yanyan Kong Lin Huang Weihao Li Xuanting Liu Yinping Zhou Cuiping Liu Shibo Zhang Fang Xie Zhengwei Zhang Donglang Jiang Weiyan Zhou Ruiqing Ni Chencheng Zhang Bomin Sun Jiao Wang Yihui Guan |
| author_facet | Yanyan Kong Lin Huang Weihao Li Xuanting Liu Yinping Zhou Cuiping Liu Shibo Zhang Fang Xie Zhengwei Zhang Donglang Jiang Weiyan Zhou Ruiqing Ni Chencheng Zhang Bomin Sun Jiao Wang Yihui Guan |
| author_sort | Yanyan Kong |
| collection | DOAJ |
| description | Alzheimer’s disease (AD), a serious neurodegenerative disease, is pathologically characterized by synaptic loss and dysfunction. Synaptic vesicle protein 2A (SV2A) is an indispensable vesicular protein specifically expressed in synapses and can be used as a biomarker for synaptic density. We found that the expression of SV2A was down-regulated in the hippocampus of AD patients, yet the relation of SV2A to other hallmarks of AD pathology such as amyloid precursor protein (APP), β-amyloid (Aβ), and Tau protein is not thoroughly clear. In addition, SV2A colocalized with APP and was down-regulated at Aβ deposition. Moreover, we found that SV2A deficiency leads to a simultaneous increase in Aβ and Tau hyperphosphorylation, while SV2A overexpression was associated with downregulation of β-site APP cleaving enzyme 1 and apolipoprotein E genes. In addition, evidence gained in the study points to the phosphatidylinositol 3-kinase signaling pathway as a possible mediator in SV2A regulation influencing the incidence and development of AD. With limited effective diagnostic methods for AD, a close interplay between SV2A and AD-related proteins demonstrated in our study may provide novel and innovative diagnostic and therapeutic opportunities. |
| first_indexed | 2024-12-15T00:50:21Z |
| format | Article |
| id | doaj.art-eefcd30982b4499fb7ed273770a1fdd4 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-15T00:50:21Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-eefcd30982b4499fb7ed273770a1fdd42022-12-21T22:41:26ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.609908609908The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for TreatmentYanyan Kong0Lin Huang1Weihao Li2Xuanting Liu3Yinping Zhou4Cuiping Liu5Shibo Zhang6Fang Xie7Zhengwei Zhang8Donglang Jiang9Weiyan Zhou10Ruiqing Ni11Chencheng Zhang12Bomin Sun13Jiao Wang14Yihui Guan15PET Center, Huashan Hospital, Fudan University, Shanghai, ChinaLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, ChinaLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, ChinaLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, ChinaLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, ChinaLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, ChinaLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, ChinaPET Center, Huashan Hospital, Fudan University, Shanghai, ChinaPET Center, Huashan Hospital, Fudan University, Shanghai, ChinaPET Center, Huashan Hospital, Fudan University, Shanghai, ChinaPET Center, Huashan Hospital, Fudan University, Shanghai, ChinaInstitute for Biomedical Engineering, ETH Zurich, University of Zurich, Zurich, SwitzerlandDepartment of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, ChinaPET Center, Huashan Hospital, Fudan University, Shanghai, ChinaAlzheimer’s disease (AD), a serious neurodegenerative disease, is pathologically characterized by synaptic loss and dysfunction. Synaptic vesicle protein 2A (SV2A) is an indispensable vesicular protein specifically expressed in synapses and can be used as a biomarker for synaptic density. We found that the expression of SV2A was down-regulated in the hippocampus of AD patients, yet the relation of SV2A to other hallmarks of AD pathology such as amyloid precursor protein (APP), β-amyloid (Aβ), and Tau protein is not thoroughly clear. In addition, SV2A colocalized with APP and was down-regulated at Aβ deposition. Moreover, we found that SV2A deficiency leads to a simultaneous increase in Aβ and Tau hyperphosphorylation, while SV2A overexpression was associated with downregulation of β-site APP cleaving enzyme 1 and apolipoprotein E genes. In addition, evidence gained in the study points to the phosphatidylinositol 3-kinase signaling pathway as a possible mediator in SV2A regulation influencing the incidence and development of AD. With limited effective diagnostic methods for AD, a close interplay between SV2A and AD-related proteins demonstrated in our study may provide novel and innovative diagnostic and therapeutic opportunities.https://www.frontiersin.org/articles/10.3389/fcell.2021.609908/fullAlzheimer’s diseaseneurodegenerationsynaptic vesicle protein 2ATauAβPI3K signaling pathway |
| spellingShingle | Yanyan Kong Lin Huang Weihao Li Xuanting Liu Yinping Zhou Cuiping Liu Shibo Zhang Fang Xie Zhengwei Zhang Donglang Jiang Weiyan Zhou Ruiqing Ni Chencheng Zhang Bomin Sun Jiao Wang Yihui Guan The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for Treatment Frontiers in Cell and Developmental Biology Alzheimer’s disease neurodegeneration synaptic vesicle protein 2A Tau Aβ PI3K signaling pathway |
| title | The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for Treatment |
| title_full | The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for Treatment |
| title_fullStr | The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for Treatment |
| title_full_unstemmed | The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for Treatment |
| title_short | The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for Treatment |
| title_sort | synaptic vesicle protein 2a interacts with key pathogenic factors in alzheimer s disease implications for treatment |
| topic | Alzheimer’s disease neurodegeneration synaptic vesicle protein 2A Tau Aβ PI3K signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.609908/full |
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