Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson’s Disease Model
The α-synuclein aggregates are the main component of Lewy bodies in Parkinson’s disease (PD) brain, and they showed immunotherapy could be employed to alleviate α-synuclein aggregate pathology in PD. Recently we have generated DNA aptamers that specifically recognize α-synuclein. In this study, we f...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253119301982 |
| _version_ | 1818591426430107648 |
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| author | Xiaoxi Ren Yun Zhao Fenqin Xue Yan Zheng Haixia Huang Wei Wang Yongchang Chang Hui Yang Jianliang Zhang |
| author_facet | Xiaoxi Ren Yun Zhao Fenqin Xue Yan Zheng Haixia Huang Wei Wang Yongchang Chang Hui Yang Jianliang Zhang |
| author_sort | Xiaoxi Ren |
| collection | DOAJ |
| description | The α-synuclein aggregates are the main component of Lewy bodies in Parkinson’s disease (PD) brain, and they showed immunotherapy could be employed to alleviate α-synuclein aggregate pathology in PD. Recently we have generated DNA aptamers that specifically recognize α-synuclein. In this study, we further investigated the in vivo effect of these aptamers on the neuropathological deficits associated with PD. For efficient delivery of the aptamers into the mouse brain, we employed modified exosomes with the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface. We demonstrated that the aptamers were efficiently packaged into the RVG-exosomes and delivered into neurons in vitro and in vivo. Functionally, the aptamer-loaded RVG-exosomes significantly reduced the α-synuclein preformed fibril (PFF)-induced pathological aggregates, and rescued synaptic protein loss and neuronal death. Moreover, intraperitoneal administration of these exosomes into the mice with intra-striatally injected α-synuclein PFF reduced the pathological α-synuclein aggregates and improved motor impairments. In conclusion, we demonstrated that the aptamers targeting α-synuclein aggregates could be effectively delivered into the mouse brain by the RVG-exosomes and reduce the neuropathological and behavioral deficits in the mouse PD model. This study highlights the therapeutic potential of the RVG-exosome delivery of aptamer to alleviate the brain α-synuclein pathology. Keywords: α-synuclein, exosomes, aptamer, Parkinson’s disease, immunotherapy |
| first_indexed | 2024-12-16T10:12:15Z |
| format | Article |
| id | doaj.art-1548b88ef52544dda614f1f321158b63 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-16T10:12:15Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-1548b88ef52544dda614f1f321158b632022-12-21T22:35:33ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-09-0117726740Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson’s Disease ModelXiaoxi Ren0Yun Zhao1Fenqin Xue2Yan Zheng3Haixia Huang4Wei Wang5Yongchang Chang6Hui Yang7Jianliang Zhang8Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing 100069, ChinaDepartment of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing 100069, ChinaCore Facilities Center, Capital Medical University, Beijing 100069, ChinaDepartment of Physiology, Capital Medical University, Beijing 100069, ChinaDepartment of Physiology, Capital Medical University, Beijing 100069, ChinaDepartment of Physiology, Capital Medical University, Beijing 100069, ChinaDivision of Neurobiology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ 85013, USADepartment of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing 100069, ChinaDepartment of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing 100069, China; Corresponding author: Jianliang Zhang, Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, #10 Xitoutiao, Youanmenwai, Beijing 100069, China.The α-synuclein aggregates are the main component of Lewy bodies in Parkinson’s disease (PD) brain, and they showed immunotherapy could be employed to alleviate α-synuclein aggregate pathology in PD. Recently we have generated DNA aptamers that specifically recognize α-synuclein. In this study, we further investigated the in vivo effect of these aptamers on the neuropathological deficits associated with PD. For efficient delivery of the aptamers into the mouse brain, we employed modified exosomes with the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface. We demonstrated that the aptamers were efficiently packaged into the RVG-exosomes and delivered into neurons in vitro and in vivo. Functionally, the aptamer-loaded RVG-exosomes significantly reduced the α-synuclein preformed fibril (PFF)-induced pathological aggregates, and rescued synaptic protein loss and neuronal death. Moreover, intraperitoneal administration of these exosomes into the mice with intra-striatally injected α-synuclein PFF reduced the pathological α-synuclein aggregates and improved motor impairments. In conclusion, we demonstrated that the aptamers targeting α-synuclein aggregates could be effectively delivered into the mouse brain by the RVG-exosomes and reduce the neuropathological and behavioral deficits in the mouse PD model. This study highlights the therapeutic potential of the RVG-exosome delivery of aptamer to alleviate the brain α-synuclein pathology. Keywords: α-synuclein, exosomes, aptamer, Parkinson’s disease, immunotherapyhttp://www.sciencedirect.com/science/article/pii/S2162253119301982 |
| spellingShingle | Xiaoxi Ren Yun Zhao Fenqin Xue Yan Zheng Haixia Huang Wei Wang Yongchang Chang Hui Yang Jianliang Zhang Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson’s Disease Model Molecular Therapy: Nucleic Acids |
| title | Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson’s Disease Model |
| title_full | Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson’s Disease Model |
| title_fullStr | Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson’s Disease Model |
| title_full_unstemmed | Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson’s Disease Model |
| title_short | Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson’s Disease Model |
| title_sort | exosomal dna aptamer targeting α synuclein aggregates reduced neuropathological deficits in a mouse parkinson s disease model |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119301982 |
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