Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration
Abstract Mammalian central nervous system (CNS) axons cannot spontaneously regenerate after injury, creating an unmet need to identify molecular regulators to promote axon regeneration and reduce the lasting impact of CNS injuries. While tubulin polymerization promoting protein family member 3 (Tppp...
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| Format: | Article |
| Language: | English |
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BMC
2024-12-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-024-01917-6 |
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| author | Mishal Rao Ziming Luo Chia-Chun Liu Chi-Yu Chen Shining Wang Michael Nahmou Bogdan Tanasa Aman Virmani Leah Byrne Jeffrey L. Goldberg José-Alain Sahel Kun-Che Chang |
| author_facet | Mishal Rao Ziming Luo Chia-Chun Liu Chi-Yu Chen Shining Wang Michael Nahmou Bogdan Tanasa Aman Virmani Leah Byrne Jeffrey L. Goldberg José-Alain Sahel Kun-Che Chang |
| author_sort | Mishal Rao |
| collection | DOAJ |
| description | Abstract Mammalian central nervous system (CNS) axons cannot spontaneously regenerate after injury, creating an unmet need to identify molecular regulators to promote axon regeneration and reduce the lasting impact of CNS injuries. While tubulin polymerization promoting protein family member 3 (Tppp3) is known to promote axon outgrowth in amphibians, its role in mammalian axon regeneration remains unknown. Here we investigated Tppp3 in retinal ganglion cells (RGCs) neuroprotection and axonal regeneration using an optic nerve crush (ONC) model in the rodent. Single-cell RNA sequencing identified the expression of Tppp3 in RGCs of mice, macaques, and humans. Tppp3 overexpression enhanced neurite outgrowth in mouse primary RGCs in vitro, promoted axon regeneration, and improved RGC survival after ONC. Bulk RNA sequencing indicated that Tppp3 overexpression upregulates axon regeneration genes such as Bmp4 and neuroinflammatory pathways. Our findings advance regenerative medicine by developing a new therapeutic strategy for RGC neuroprotection and axon regeneration. |
| format | Article |
| id | doaj-art-baf4869505b444e4914abd74afc8a297 |
| institution | Kabale University |
| issn | 2051-5960 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-baf4869505b444e4914abd74afc8a2972025-01-05T12:49:39ZengBMCActa Neuropathologica Communications2051-59602024-12-0112111610.1186/s40478-024-01917-6Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regenerationMishal Rao0Ziming Luo1Chia-Chun Liu2Chi-Yu Chen3Shining Wang4Michael Nahmou5Bogdan Tanasa6Aman Virmani7Leah Byrne8Jeffrey L. Goldberg9José-Alain Sahel10Kun-Che Chang11Department of Ophthalmology, UPMC Vision Institute, University of Pittsburgh School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford UniversityDepartment of Ophthalmology, UPMC Vision Institute, University of Pittsburgh School of MedicineDepartment of Ophthalmology, UPMC Vision Institute, University of Pittsburgh School of MedicineDepartment of Ophthalmology, UPMC Vision Institute, University of Pittsburgh School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford UniversitySpencer Center for Vision Research, Byers Eye Institute, Stanford UniversityDepartment of Ophthalmology, UPMC Vision Institute, University of Pittsburgh School of MedicineDepartment of Ophthalmology, UPMC Vision Institute, University of Pittsburgh School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford UniversityDepartment of Ophthalmology, UPMC Vision Institute, University of Pittsburgh School of MedicineDepartment of Ophthalmology, UPMC Vision Institute, University of Pittsburgh School of MedicineAbstract Mammalian central nervous system (CNS) axons cannot spontaneously regenerate after injury, creating an unmet need to identify molecular regulators to promote axon regeneration and reduce the lasting impact of CNS injuries. While tubulin polymerization promoting protein family member 3 (Tppp3) is known to promote axon outgrowth in amphibians, its role in mammalian axon regeneration remains unknown. Here we investigated Tppp3 in retinal ganglion cells (RGCs) neuroprotection and axonal regeneration using an optic nerve crush (ONC) model in the rodent. Single-cell RNA sequencing identified the expression of Tppp3 in RGCs of mice, macaques, and humans. Tppp3 overexpression enhanced neurite outgrowth in mouse primary RGCs in vitro, promoted axon regeneration, and improved RGC survival after ONC. Bulk RNA sequencing indicated that Tppp3 overexpression upregulates axon regeneration genes such as Bmp4 and neuroinflammatory pathways. Our findings advance regenerative medicine by developing a new therapeutic strategy for RGC neuroprotection and axon regeneration.https://doi.org/10.1186/s40478-024-01917-6Tppp3Retinal ganglion cellsAxon regenerationNeurite outgrowthBMP4Inflammation |
| spellingShingle | Mishal Rao Ziming Luo Chia-Chun Liu Chi-Yu Chen Shining Wang Michael Nahmou Bogdan Tanasa Aman Virmani Leah Byrne Jeffrey L. Goldberg José-Alain Sahel Kun-Che Chang Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration Acta Neuropathologica Communications Tppp3 Retinal ganglion cells Axon regeneration Neurite outgrowth BMP4 Inflammation |
| title | Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration |
| title_full | Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration |
| title_fullStr | Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration |
| title_full_unstemmed | Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration |
| title_short | Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration |
| title_sort | tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration |
| topic | Tppp3 Retinal ganglion cells Axon regeneration Neurite outgrowth BMP4 Inflammation |
| url | https://doi.org/10.1186/s40478-024-01917-6 |
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