Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction
Botulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is di...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2015-12-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6651/7/12/4887 |
| _version_ | 1828370479529852928 |
|---|---|
| author | Elisa Duregotti Giulia Zanetti Michele Scorzeto Aram Megighian Cesare Montecucco Marco Pirazzini Michela Rigoni |
| author_facet | Elisa Duregotti Giulia Zanetti Michele Scorzeto Aram Megighian Cesare Montecucco Marco Pirazzini Michela Rigoni |
| author_sort | Elisa Duregotti |
| collection | DOAJ |
| description | Botulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body. |
| first_indexed | 2024-04-14T06:38:40Z |
| format | Article |
| id | doaj.art-b1066d915215496b96a8164a96602922 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-14T06:38:40Z |
| publishDate | 2015-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-b1066d915215496b96a8164a966029222022-12-22T02:07:24ZengMDPI AGToxins2072-66512015-12-017125322533610.3390/toxins7124887toxins7124887Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular JunctionElisa Duregotti0Giulia Zanetti1Michele Scorzeto2Aram Megighian3Cesare Montecucco4Marco Pirazzini5Michela Rigoni6Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, ItalyBotulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body.http://www.mdpi.com/2072-6651/7/12/4887botulinum neurotoxinsanimal neurotoxinsnerve terminals degenerationmouseDAS assayparalysisneuroexocytosis |
| spellingShingle | Elisa Duregotti Giulia Zanetti Michele Scorzeto Aram Megighian Cesare Montecucco Marco Pirazzini Michela Rigoni Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction Toxins botulinum neurotoxins animal neurotoxins nerve terminals degeneration mouse DAS assay paralysis neuroexocytosis |
| title | Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction |
| title_full | Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction |
| title_fullStr | Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction |
| title_full_unstemmed | Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction |
| title_short | Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction |
| title_sort | snake and spider toxins induce a rapid recovery of function of botulinum neurotoxin paralysed neuromuscular junction |
| topic | botulinum neurotoxins animal neurotoxins nerve terminals degeneration mouse DAS assay paralysis neuroexocytosis |
| url | http://www.mdpi.com/2072-6651/7/12/4887 |
| work_keys_str_mv | AT elisaduregotti snakeandspidertoxinsinducearapidrecoveryoffunctionofbotulinumneurotoxinparalysedneuromuscularjunction AT giuliazanetti snakeandspidertoxinsinducearapidrecoveryoffunctionofbotulinumneurotoxinparalysedneuromuscularjunction AT michelescorzeto snakeandspidertoxinsinducearapidrecoveryoffunctionofbotulinumneurotoxinparalysedneuromuscularjunction AT arammegighian snakeandspidertoxinsinducearapidrecoveryoffunctionofbotulinumneurotoxinparalysedneuromuscularjunction AT cesaremontecucco snakeandspidertoxinsinducearapidrecoveryoffunctionofbotulinumneurotoxinparalysedneuromuscularjunction AT marcopirazzini snakeandspidertoxinsinducearapidrecoveryoffunctionofbotulinumneurotoxinparalysedneuromuscularjunction AT michelarigoni snakeandspidertoxinsinducearapidrecoveryoffunctionofbotulinumneurotoxinparalysedneuromuscularjunction |