Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regeneration
Nogo receptor 1 (NgR1) mediates the inhibitory effects of several myelin-associated inhibitors (MAIs) on axonal regeneration in the central nervous system. A truncated soluble NgR1 (sNgR) has been reported to act as a decoy receptor to block the actions of MAIs. In this study, we fused the sNgR to n...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-10-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996113001824 |
| _version_ | 1831586390185345024 |
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| author | Yi Zhang Fangyou Gao Dongsheng Wu Pouria Moshayedi Xinyu Zhang Habib Ellamushi John Yeh John V. Priestley Xuenong Bo |
| author_facet | Yi Zhang Fangyou Gao Dongsheng Wu Pouria Moshayedi Xinyu Zhang Habib Ellamushi John Yeh John V. Priestley Xuenong Bo |
| author_sort | Yi Zhang |
| collection | DOAJ |
| description | Nogo receptor 1 (NgR1) mediates the inhibitory effects of several myelin-associated inhibitors (MAIs) on axonal regeneration in the central nervous system. A truncated soluble NgR1 (sNgR) has been reported to act as a decoy receptor to block the actions of MAIs. In this study, we fused the sNgR to nerve growth factor (NGF) and used NGF as a carrier to deliver sNgR to the intercellular space to neutralize MAIs. NGF in NGF–sNgR remained biologically active and induced sprouting of calcitonin gene related peptide containing axons when expressed in the spinal cord using a lentiviral vector (LV). Secreted NGF–sNgR promoted neurite outgrowth of dissociated dorsal root ganglion neurons on myelin protein substrate. In a rat dorsal column transection model, regenerating sensory axons were found to grow into the lesion cavity in animals injected with LV/NGF–sNgR, while in animals injected with LV/GFP or LV/NGF–GFP few sensory axons entered the lesion cavity. The results indicate that NGF–sNgR fusion protein can reduce the inhibition of MAIs and facilitate sensory axon regeneration. The fusion constructs may be modified to target other molecules to promote axonal regeneration and the concept may also be adapted to develop gene therapy strategies to treat other disorders. |
| first_indexed | 2024-12-17T21:35:32Z |
| format | Article |
| id | doaj.art-65c5ea46c1d84680bd586717959e61d4 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T21:35:32Z |
| publishDate | 2013-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-65c5ea46c1d84680bd586717959e61d42022-12-21T21:31:45ZengElsevierNeurobiology of Disease1095-953X2013-10-0158270280Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regenerationYi Zhang0Fangyou Gao1Dongsheng Wu2Pouria Moshayedi3Xinyu Zhang4Habib Ellamushi5John Yeh6John V. Priestley7Xuenong Bo8Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UKCentre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Department of Neurosurgery, Guizhou Provincial Hospital, Guiyang, ChinaCentre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UKCentre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UKCentre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UKCentre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Department of Neurosurgery, Royal London Hospital, London, UKCentre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Department of Neurosurgery, Royal London Hospital, London, UKCentre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UKCentre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Corresponding author at: Centre for Neuroscience and Trauma, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, Whitechapel, London E1 2AT, UK. Fax: +44 20 78822180.Nogo receptor 1 (NgR1) mediates the inhibitory effects of several myelin-associated inhibitors (MAIs) on axonal regeneration in the central nervous system. A truncated soluble NgR1 (sNgR) has been reported to act as a decoy receptor to block the actions of MAIs. In this study, we fused the sNgR to nerve growth factor (NGF) and used NGF as a carrier to deliver sNgR to the intercellular space to neutralize MAIs. NGF in NGF–sNgR remained biologically active and induced sprouting of calcitonin gene related peptide containing axons when expressed in the spinal cord using a lentiviral vector (LV). Secreted NGF–sNgR promoted neurite outgrowth of dissociated dorsal root ganglion neurons on myelin protein substrate. In a rat dorsal column transection model, regenerating sensory axons were found to grow into the lesion cavity in animals injected with LV/NGF–sNgR, while in animals injected with LV/GFP or LV/NGF–GFP few sensory axons entered the lesion cavity. The results indicate that NGF–sNgR fusion protein can reduce the inhibition of MAIs and facilitate sensory axon regeneration. The fusion constructs may be modified to target other molecules to promote axonal regeneration and the concept may also be adapted to develop gene therapy strategies to treat other disorders.http://www.sciencedirect.com/science/article/pii/S0969996113001824Nogo receptorNerve growth factorSpinal cord injuryAxon regenerationLentiviral vectorGene therapy |
| spellingShingle | Yi Zhang Fangyou Gao Dongsheng Wu Pouria Moshayedi Xinyu Zhang Habib Ellamushi John Yeh John V. Priestley Xuenong Bo Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regeneration Neurobiology of Disease Nogo receptor Nerve growth factor Spinal cord injury Axon regeneration Lentiviral vector Gene therapy |
| title | Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regeneration |
| title_full | Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regeneration |
| title_fullStr | Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regeneration |
| title_full_unstemmed | Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regeneration |
| title_short | Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regeneration |
| title_sort | lentiviral mediated expression of a ngf soluble nogo receptor 1 fusion protein promotes axonal regeneration |
| topic | Nogo receptor Nerve growth factor Spinal cord injury Axon regeneration Lentiviral vector Gene therapy |
| url | http://www.sciencedirect.com/science/article/pii/S0969996113001824 |
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