The binding of botulinum neurotoxins to different peripheral neurons

Rossetto, Ornella

doi:10.1016/j.toxicon.2017.10.010

Cited by 11 publications

(8 citation statements)

References 68 publications

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“…La partie C-terminale de la chaîne H (HC) est organisée en deux sous-domaines distincts (HCN et HCC). Le domaine HCC est impliqué dans la reconnaissance des récepteurs membranaires ( §4.2) des BoNT (pour revue [17][18][19]). La liaison de la BoNT à la membrane neuronale (Fig.…”

Section: Les Neurotoxines Botuliquesunclassified

“…La liaison de la BoNT à la membrane neuronale (Fig. 1Ba) implique le domaine le plus C-terminal (HCC) de sa chaîne lourde (pour revues [18][19]). Récemment le domaine HCN a aussi été impliqué dans la liaison de la BoNT [20].…”

Section: Les Neurotoxines Botuliquesunclassified

“…Les synaptotagmines I et II (Syt I, Syt II) servent de récepteur protéique aux BoNT/B, /DC et /G (pour revue [8,[18][19]). Les Syt-I et Syt-II détectent l'élévation de la concentration calcique et répondent à ce signal en déclenchant les dernières étapes de fusion des vésicules synaptiques avec la membrane plasmique synaptiques (pour revue [23].…”

Section: La Synaptotagmine Est Un Récepteur Protéique Pour La Bont/bunclassified

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Neurotoxine botulique : mécanismes moléculaires et cellulaires de son action sur le système nerveux

Poulain

Popoff

2020

Bulletin de l'Académie Nationale de Médecine

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Botulinum toxins are protein complexes comprised of a neuroactive protein, botulinum neurotoxin (BoNT), and several non-toxic associated proteins. All medical indications for botulinum toxins are based on the very long-term inhibitory action of BoNT on the release of neurotransmitter. BoNT is a 150 kDa protein that binds to nerve endings, is internalized in them and blocks the vesicular neurotransmitter exocytosis machinery. Depending on its serotype, BoNT cleaves one among the three SNARE proteins involved in the fusion of synaptic vesicles with the plasma membrane of nerve endings, regardless of the type of transmitter they contain. The very high selectivity of action of BoNT for neuron nerve terminals is mainly due to its binding a protein receptor (synaptotagmin or SV2, depending on the BoNT serotype), which is a synaptic vesicle membrane protein exposed on the surface of neuron terminations during neurotransmitter exocytosis. BoNT cannot cross the blood-brain barrier, therefore, its effects are mainly peripheral. Nevertheless, after an injection of BoNT in the periphery, the neurotoxin captured by the peripheral nerve endings can be retrogradely transported inside sensory neurons where it can act, thereby modifying sensory information ascending to the central nervous system. The neuronal specificity of BoNT makes it a therapeutic tool used in a wide range of indications in physical and rehabilitation medicine, neurology, ophthalmology, urology and pain management.

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Section: Les Neurotoxines Botuliquesunclassified

Section: La Synaptotagmine Est Un Récepteur Protéique Pour La Bont/bunclassified

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Neurotoxine botulique : mécanismes moléculaires et cellulaires de son action sur le système nerveux

Poulain

Popoff

2020

Bulletin de l'Académie Nationale de Médecine

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“…Furthermore, injecting Botox, a medication that blocks the ACh-R, into a psoriatic plaque results in clearing of only that lesion. 23,24 For unknown reasons, individuals with Pso have a significantly higher risk of developing MS and the more severe the Pso is, the more likely the individual will develop MS. 25 Furthermore, TNFa inhibitors can worsen the symptoms of MS and can even induce this disease. 26 Also, these drugs can induce Pso.…”

Section: Psoriasismentioning

confidence: 99%

The Relationship of Wound Healing with Psoriasis and Multiple Sclerosis

Morhenn

2018

Advances in Wound Care

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Better understanding of wound healing could lead to improved treatment(s) of multiple sclerosis (MS) and psoriasis (Pso). New concepts in the events of wound healing, such as the roles of the innate and adaptive immune systems, have generated targets for treating these debilitating diseases. That in MS and Pso defective wound healing is responsible for the diseases' progression has not been hypothesized to date. Impaired initiation of wound repair by oligodendrocyte precursor cells or oligodendrocytes may play a role in MS, and a lack of inhibition of the proliferative phase in wound healing may explain the pathophysiology involved in Pso.

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“…In addition to motor-neurons, BoNTs enter various peripheral neurons. BoNT/A can block cholinergic pre-and post-ganglionic nerve terminals of the parasympathetic and sympathetic autonomic nervous system thus affecting smooth muscle and secretion and leading to autonomic dysfunction (rev in (Rossetto, 2018). The parasympathetic nervous system consists of a first peripheral preganglionic cholinergic neuron connected by myelinated axon to a second post-ganglionic cholinergic neuron innervating the effector organ.…”

Section: -2 Bonts and The Autonomic Nervous Systemmentioning

confidence: 99%

Neuronal selectivity of botulinum neurotoxins

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2018

Toxicon

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Botulinum neurotoxins (BoNTs) are highly potent toxins responsible for a severe disease, called botulism. They are also efficient therapeutic tools with an increasing number of indications ranging from neuromuscular dysfunction to hypersecretion syndrome, pain release, depression as well as cosmetic application. BoNTs are known to mainly target motorneuron endings and to induce flaccid paralysis. BoNTs recognize a specific double receptor on neuronal cells consisting of gangliosides and synaptic vesicle protein, SV2 or synaptotagmin. Using cultured neuronal cells, BoNTs have been established blocking the release of a wide variety of neurotransmitters. However, BoNTs are more potent in motorneurons than in the other neuronal cell types. In in vivo models, BoNT/A impairs the cholinergic neuronal transmission at the motor-neurons but also at neurons controlling secretions and smooth muscle neurons, and blocks several neuronal pathways including excitatory, inhibitory, and sensitive neurons. However, only a few reports investigated the neuronal selectivity of BoNTs in vivo. In the intestinal wall, BoNT/A and BoNT/B target mainly the cholinergic neurons and to a lower extent the other non-cholinergic neurons including serotonergic, glutamatergic, GABAergic, and VIP-neurons. The in vivo effects induced by BoNTs on the non-cholinergic neurons remain to be precisely investigated. We report here a literature review of the neuronal selectivity of BoNTs.

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The binding of botulinum neurotoxins to different peripheral neurons

Cited by 11 publications

References 68 publications

Neurotoxine botulique : mécanismes moléculaires et cellulaires de son action sur le système nerveux

Neurotoxine botulique : mécanismes moléculaires et cellulaires de son action sur le système nerveux

The Relationship of Wound Healing with Psoriasis and Multiple Sclerosis

Neuronal selectivity of botulinum neurotoxins

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