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Recovery from the Neuroparalysis Caused by the Micrurus nigrocinctus Venom Is Accelerated by an Agonist of the CXCR4 Receptor

Snake envenoming is a major but neglected human disease in tropical and subtropical regions. Among venomous snakes in the Americas, coral snakes of the genus Micrurus are particularly dangerous because they cause a peripheral neuroparalysis that can persist for many days or, in severe cases, progres...

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Autores principales: Stazi, Marco, Fabris, Federico, Fernández, Julián, D’Este, Giorgia, Rigoni, Michela, Megighian, Aram, Gutiérrez, José María, Lomonte, Bruno, Montecucco, Cesare
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412299/
https://www.ncbi.nlm.nih.gov/pubmed/36006193
http://dx.doi.org/10.3390/toxins14080531
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author Stazi, Marco
Fabris, Federico
Fernández, Julián
D’Este, Giorgia
Rigoni, Michela
Megighian, Aram
Gutiérrez, José María
Lomonte, Bruno
Montecucco, Cesare
author_facet Stazi, Marco
Fabris, Federico
Fernández, Julián
D’Este, Giorgia
Rigoni, Michela
Megighian, Aram
Gutiérrez, José María
Lomonte, Bruno
Montecucco, Cesare
author_sort Stazi, Marco
collection PubMed
description Snake envenoming is a major but neglected human disease in tropical and subtropical regions. Among venomous snakes in the Americas, coral snakes of the genus Micrurus are particularly dangerous because they cause a peripheral neuroparalysis that can persist for many days or, in severe cases, progress to death. Ventilatory support and the use of snake species-specific antivenoms may prevent death from respiratory paralysis in most cases. However, there is a general consensus that additional and non-expensive treatments that can be delivered even long after the snake bite are needed. Neurotoxic degeneration of peripheral motor neurons activates pro-regenerative intercellular signaling programs, the greatest of which consist of the chemokine CXCL12α, produced by perisynaptic Schwann cells, which act on the CXCR4 receptor expressed on damaged neuronal axons. We recently found that the CXCR4 agonist NUCC-390 promotes axonal growth. Here, we show that the venom of the highly neurotoxic snake Micrurus nigrocinctus causes a complete degeneration of motor axon terminals of the soleus muscle, followed by functional regeneration whose time course is greatly accelerated by NUCC-390. These results suggest that NUCC-390 is a potential candidate for treating human patients envenomed by Micrurus nigrocinctus as well as other neurotoxic Micrurus spp. in order to improve the recovery of normal neuromuscular physiology, thus reducing the mortality and hospital costs of envenoming.
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spelling pubmed-94122992022-08-27 Recovery from the Neuroparalysis Caused by the Micrurus nigrocinctus Venom Is Accelerated by an Agonist of the CXCR4 Receptor Stazi, Marco Fabris, Federico Fernández, Julián D’Este, Giorgia Rigoni, Michela Megighian, Aram Gutiérrez, José María Lomonte, Bruno Montecucco, Cesare Toxins (Basel) Article Snake envenoming is a major but neglected human disease in tropical and subtropical regions. Among venomous snakes in the Americas, coral snakes of the genus Micrurus are particularly dangerous because they cause a peripheral neuroparalysis that can persist for many days or, in severe cases, progress to death. Ventilatory support and the use of snake species-specific antivenoms may prevent death from respiratory paralysis in most cases. However, there is a general consensus that additional and non-expensive treatments that can be delivered even long after the snake bite are needed. Neurotoxic degeneration of peripheral motor neurons activates pro-regenerative intercellular signaling programs, the greatest of which consist of the chemokine CXCL12α, produced by perisynaptic Schwann cells, which act on the CXCR4 receptor expressed on damaged neuronal axons. We recently found that the CXCR4 agonist NUCC-390 promotes axonal growth. Here, we show that the venom of the highly neurotoxic snake Micrurus nigrocinctus causes a complete degeneration of motor axon terminals of the soleus muscle, followed by functional regeneration whose time course is greatly accelerated by NUCC-390. These results suggest that NUCC-390 is a potential candidate for treating human patients envenomed by Micrurus nigrocinctus as well as other neurotoxic Micrurus spp. in order to improve the recovery of normal neuromuscular physiology, thus reducing the mortality and hospital costs of envenoming. MDPI 2022-08-02 /pmc/articles/PMC9412299/ /pubmed/36006193 http://dx.doi.org/10.3390/toxins14080531 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Stazi, Marco
Fabris, Federico
Fernández, Julián
D’Este, Giorgia
Rigoni, Michela
Megighian, Aram
Gutiérrez, José María
Lomonte, Bruno
Montecucco, Cesare
Recovery from the Neuroparalysis Caused by the Micrurus nigrocinctus Venom Is Accelerated by an Agonist of the CXCR4 Receptor
title Recovery from the Neuroparalysis Caused by the Micrurus nigrocinctus Venom Is Accelerated by an Agonist of the CXCR4 Receptor
title_full Recovery from the Neuroparalysis Caused by the Micrurus nigrocinctus Venom Is Accelerated by an Agonist of the CXCR4 Receptor
title_fullStr Recovery from the Neuroparalysis Caused by the Micrurus nigrocinctus Venom Is Accelerated by an Agonist of the CXCR4 Receptor
title_full_unstemmed Recovery from the Neuroparalysis Caused by the Micrurus nigrocinctus Venom Is Accelerated by an Agonist of the CXCR4 Receptor
title_short Recovery from the Neuroparalysis Caused by the Micrurus nigrocinctus Venom Is Accelerated by an Agonist of the CXCR4 Receptor
title_sort recovery from the neuroparalysis caused by the micrurus nigrocinctus venom is accelerated by an agonist of the cxcr4 receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412299/
https://www.ncbi.nlm.nih.gov/pubmed/36006193
http://dx.doi.org/10.3390/toxins14080531
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