Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit
Abstract Cerebrovascular dysfunction characterized by the neurovascular unit (NVU) impairment contributes to the pathogenesis of Alzheimer's disease (AD). In this study, a cerebrovascular‐targeting multifunctional lipoprotein‐biomimetic nanostructure (RAP‐RL) constituted with an antagonist pept...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202001918 |
| _version_ | 1797946755783852032 |
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| author | Qian Zhang Qingxiang Song Xiao Gu Mengna Zheng Antian Wang Gan Jiang Meng Huang Huan Chen Yu Qiu Bin Bo Shanbao Tong Rong Shao Binyin Li Gang Wang Hao Wang Yongbo Hu Hongzhuan Chen Xiaoling Gao |
| author_facet | Qian Zhang Qingxiang Song Xiao Gu Mengna Zheng Antian Wang Gan Jiang Meng Huang Huan Chen Yu Qiu Bin Bo Shanbao Tong Rong Shao Binyin Li Gang Wang Hao Wang Yongbo Hu Hongzhuan Chen Xiaoling Gao |
| author_sort | Qian Zhang |
| collection | DOAJ |
| description | Abstract Cerebrovascular dysfunction characterized by the neurovascular unit (NVU) impairment contributes to the pathogenesis of Alzheimer's disease (AD). In this study, a cerebrovascular‐targeting multifunctional lipoprotein‐biomimetic nanostructure (RAP‐RL) constituted with an antagonist peptide (RAP) of receptor for advanced glycation end‐products (RAGE), monosialotetrahexosyl ganglioside, and apolipoprotein E3 is developed to recover the functional NVU and normalize the cerebral vasculature. RAP‐RL accumulates along the cerebral microvasculature through the specific binding of RAP to RAGE, which is overexpressed on cerebral endothelial cells in AD. It effectively accelerates the clearance of perivascular Aβ, normalizes the morphology and functions of cerebrovasculature, and restores the structural integrity and functions of NVU. RAP‐RL markedly rescues the spatial learning and memory in APP/PS1 mice. Collectively, this study demonstrates the potential of the multifunctional nanostructure RAP‐RL as a disease‐modifying modality for AD treatment and provides the proof of concept that remodeling the functional NVU may represent a promising therapeutic approach toward effective intervention of AD. |
| first_indexed | 2024-04-10T21:16:03Z |
| format | Article |
| id | doaj.art-22385230ba9a4170aef1308fc00807ca |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-10T21:16:03Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-22385230ba9a4170aef1308fc00807ca2023-01-20T12:20:39ZengWileyAdvanced Science2198-38442021-01-0182n/an/a10.1002/advs.202001918Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular UnitQian Zhang0Qingxiang Song1Xiao Gu2Mengna Zheng3Antian Wang4Gan Jiang5Meng Huang6Huan Chen7Yu Qiu8Bin Bo9Shanbao Tong10Rong Shao11Binyin Li12Gang Wang13Hao Wang14Yongbo Hu15Hongzhuan Chen16Xiaoling Gao17Department of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaSchool of Biomedical Engineering and Med‐X Research Institute Shanghai Jiao Tong University 800 Dongchuan Road Shanghai 200240 ChinaSchool of Biomedical Engineering and Med‐X Research Institute Shanghai Jiao Tong University 800 Dongchuan Road Shanghai 200240 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Neurology & Neuroscience Institute Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine 197 Rui Jin Er Road Shanghai 200025 ChinaDepartment of Neurology & Neuroscience Institute Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine 197 Rui Jin Er Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaDepartment of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related Genes Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 ChinaAbstract Cerebrovascular dysfunction characterized by the neurovascular unit (NVU) impairment contributes to the pathogenesis of Alzheimer's disease (AD). In this study, a cerebrovascular‐targeting multifunctional lipoprotein‐biomimetic nanostructure (RAP‐RL) constituted with an antagonist peptide (RAP) of receptor for advanced glycation end‐products (RAGE), monosialotetrahexosyl ganglioside, and apolipoprotein E3 is developed to recover the functional NVU and normalize the cerebral vasculature. RAP‐RL accumulates along the cerebral microvasculature through the specific binding of RAP to RAGE, which is overexpressed on cerebral endothelial cells in AD. It effectively accelerates the clearance of perivascular Aβ, normalizes the morphology and functions of cerebrovasculature, and restores the structural integrity and functions of NVU. RAP‐RL markedly rescues the spatial learning and memory in APP/PS1 mice. Collectively, this study demonstrates the potential of the multifunctional nanostructure RAP‐RL as a disease‐modifying modality for AD treatment and provides the proof of concept that remodeling the functional NVU may represent a promising therapeutic approach toward effective intervention of AD.https://doi.org/10.1002/advs.202001918Alzheimer's diseasecerebrovasculaturemultifunctional nanostructureNVU remodeling |
| spellingShingle | Qian Zhang Qingxiang Song Xiao Gu Mengna Zheng Antian Wang Gan Jiang Meng Huang Huan Chen Yu Qiu Bin Bo Shanbao Tong Rong Shao Binyin Li Gang Wang Hao Wang Yongbo Hu Hongzhuan Chen Xiaoling Gao Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit Advanced Science Alzheimer's disease cerebrovasculature multifunctional nanostructure NVU remodeling |
| title | Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit |
| title_full | Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit |
| title_fullStr | Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit |
| title_full_unstemmed | Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit |
| title_short | Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit |
| title_sort | multifunctional nanostructure rap rl rescues alzheimer s cognitive deficits through remodeling the neurovascular unit |
| topic | Alzheimer's disease cerebrovasculature multifunctional nanostructure NVU remodeling |
| url | https://doi.org/10.1002/advs.202001918 |
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