Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies
Neural Regeneration Research: Impact Factor 2022: 6.1
| Main Authors: | , , , , , |
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| Format: | info:eu-repo/semantics/publishedVersion |
| Language: | eng |
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Chinese Association of Rehabilitation Medicine
2024
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| Subjects: | |
| Online Access: | http://hdl.handle.net/11086/552350 https://journals.lww.com/nrronline/fulltext/2024/04000/blockade_of_rho_associated_kinase_prevents.35.aspx |
| _version_ | 1802926364125298688 |
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| author | Berardo, Andrés Bacaglio, Cristian R. Báez, Bárbara B. Sambuelli, Rubén Sheikh, Kazim A. Lopez, Pablo H. H. |
| author2 | https://orcid.org/0000-0003-0702-2117 |
| author_facet | https://orcid.org/0000-0003-0702-2117 Berardo, Andrés Bacaglio, Cristian R. Báez, Bárbara B. Sambuelli, Rubén Sheikh, Kazim A. Lopez, Pablo H. H. |
| author_sort | Berardo, Andrés |
| collection | Repositorio Digital Universitario |
| description | Neural Regeneration Research: Impact Factor 2022: 6.1 |
| format | info:eu-repo/semantics/publishedVersion |
| id | rdu-unc.552350 |
| institution | Universidad Nacional de Cordoba |
| language | eng |
| publishDate | 2024 |
| publisher | Chinese Association of Rehabilitation Medicine |
| record_format | dspace |
| spelling | rdu-unc.5523502024-06-24T14:01:26Z Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies Berardo, Andrés Bacaglio, Cristian R. Báez, Bárbara B. Sambuelli, Rubén Sheikh, Kazim A. Lopez, Pablo H. H. https://orcid.org/0000-0003-0702-2117 https://orcid.org/0000-0003-2263-1500 https://orcid.org/0000-0003-4959-6792 Anti-ganglioside antibodies Anti-glycan antibodies Axon regeneration Ganglioside Guillain-Barré syndrome Nerve repair ROCK Y-27632 Neural Regeneration Research: Impact Factor 2022: 6.1 info:eu-repo/semantics/publishedVersion Fil: Berardo, Andrés. Universidad Nacional de Córdoba, Córdoba, Argentina. Fil: Berardo, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martin Ferreyra. Laboratorio de Neurobiología, Argentina. Fil: Bacaglio, Cristian R. Universidad Nacional de Córdoba, Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Argentina. Fil: Bacaglio, Cristian R. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. Fil: Bacaglio, Cristian R. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martin Ferreyra. Laboratorio de Neurobiología, Argentina. Fil: Báez, Bárbara B. Universidad Nacional de Córdoba, Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Argentina. Fil: Báez, Bárbara B. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. Fil: Báez, Bárbara B. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martin Ferreyra. Laboratorio de Neurobiología, Argentina. Fil: Sambuelli, Rubén. Universidad Católica de Córdoba. Clínica Universitaria Reina Fabiola. Servicio de Anatomía Patológica, Argentina. Fil: Sheikh, Kazim A. University of Texas. Medical School at Houston. Department of Neurology, Texas, United States of America. Fil: Lopez, Pablo H. H. Universidad Nacional de Córdoba, Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Argentina. Fil: Lopez, Pablo H. H. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. Fil: Lopez, Pablo H. H. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martin Ferreyra. Laboratorio de Neurobiología, Argentina. Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrè syndrome, mostly related to halted axon regeneration. Crosslinking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration. These effects involve the activation of the small GTPase RhoA/ROCK signaling pathways, which negatively modulate growth cone cytoskeleton, similarly to well stablished inhibitors of axon regeneration described so far. The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632, a selective pharmacological inhibitor of ROCK, in a mouse model of axon regeneration of peripheral nerves, where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers. Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632. Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity. In contrast, the same dose showed toxic effects on the regeneration of myelinated fibers. Interestingly, scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632. Overall, these findings confirm the in vivo participation of RhoA/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody. Our findings open the possibility of therapeutic pharmacological intervention targeting RhoA/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system. info:eu-repo/semantics/publishedVersion Fil: Berardo, Andrés. Universidad Nacional de Córdoba, Córdoba, Argentina. Fil: Berardo, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martin Ferreyra. Laboratorio de Neurobiología, Argentina. Fil: Bacaglio, Cristian R. Universidad Nacional de Córdoba, Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Argentina. Fil: Bacaglio, Cristian R. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. Fil: Bacaglio, Cristian R. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martin Ferreyra. Laboratorio de Neurobiología, Argentina. Fil: Báez, Bárbara B. Universidad Nacional de Córdoba, Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Argentina. Fil: Báez, Bárbara B. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. Fil: Báez, Bárbara B. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martin Ferreyra. Laboratorio de Neurobiología, Argentina. Fil: Sambuelli, Rubén. Universidad Católica de Córdoba. Clínica Universitaria Reina Fabiola. Servicio de Anatomía Patológica, Argentina. Fil: Sheikh, Kazim A. University of Texas. Medical School at Houston. Department of Neurology, Texas, United States of America. Fil: Lopez, Pablo H. H. Universidad Nacional de Córdoba, Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Argentina. Fil: Lopez, Pablo H. H. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. Fil: Lopez, Pablo H. H. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martin Ferreyra. Laboratorio de Neurobiología, Argentina. 2024-06-20T03:25:03Z 2024-06-20T03:25:03Z 2024-04 article Berardo, A., Bacaglio, C. R., Báez, B. B., Sambuelli, R., Sheikh, K. A., & Lopez, , P. H. H. (2024). Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies. Neural Regeneration Research, 19 (4), 895-899. https://doi.org/DOI: 10.4103/1673-5374.382258 1673-5374 http://hdl.handle.net/11086/552350 1876-7958 https://journals.lww.com/nrronline/fulltext/2024/04000/blockade_of_rho_associated_kinase_prevents.35.aspx DOI: 10.4103/1673-5374.382258 eng Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ Chinese Association of Rehabilitation Medicine |
| spellingShingle | Anti-ganglioside antibodies Anti-glycan antibodies Axon regeneration Ganglioside Guillain-Barré syndrome Nerve repair ROCK Y-27632 Berardo, Andrés Bacaglio, Cristian R. Báez, Bárbara B. Sambuelli, Rubén Sheikh, Kazim A. Lopez, Pablo H. H. Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies |
| title | Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies |
| title_full | Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies |
| title_fullStr | Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies |
| title_full_unstemmed | Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies |
| title_short | Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies |
| title_sort | blockade of rho associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti ganglioside antibodies |
| topic | Anti-ganglioside antibodies Anti-glycan antibodies Axon regeneration Ganglioside Guillain-Barré syndrome Nerve repair ROCK Y-27632 |
| url | http://hdl.handle.net/11086/552350 https://journals.lww.com/nrronline/fulltext/2024/04000/blockade_of_rho_associated_kinase_prevents.35.aspx |
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