Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1784775459792224256 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9412299 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT stazimarco recoveryfromtheneuroparalysiscausedbythemicrurusnigrocinctusvenomisacceleratedbyanagonistofthecxcr4receptor AT fabrisfederico recoveryfromtheneuroparalysiscausedbythemicrurusnigrocinctusvenomisacceleratedbyanagonistofthecxcr4receptor AT fernandezjulian recoveryfromtheneuroparalysiscausedbythemicrurusnigrocinctusvenomisacceleratedbyanagonistofthecxcr4receptor AT destegiorgia recoveryfromtheneuroparalysiscausedbythemicrurusnigrocinctusvenomisacceleratedbyanagonistofthecxcr4receptor AT rigonimichela recoveryfromtheneuroparalysiscausedbythemicrurusnigrocinctusvenomisacceleratedbyanagonistofthecxcr4receptor AT megighianaram recoveryfromtheneuroparalysiscausedbythemicrurusnigrocinctusvenomisacceleratedbyanagonistofthecxcr4receptor AT gutierrezjosemaria recoveryfromtheneuroparalysiscausedbythemicrurusnigrocinctusvenomisacceleratedbyanagonistofthecxcr4receptor AT lomontebruno recoveryfromtheneuroparalysiscausedbythemicrurusnigrocinctusvenomisacceleratedbyanagonistofthecxcr4receptor AT montecuccocesare recoveryfromtheneuroparalysiscausedbythemicrurusnigrocinctusvenomisacceleratedbyanagonistofthecxcr4receptor |