Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip

Abstract

Botulinum neurotoxins (BoNTs), the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

Structural Insights into Rational Design of Single-Domain Antibody-Based Antitoxins against Botulinum Neurotoxins

“…BoNT exposure inhibits the release of acetylcholine in presynaptic neurons, leading to a flaccid neuromuscular paralysis that causes death by respiratory collapse. There are seven classical BoNT serotypes (designated A through G), with several new BoNT or BoNT-like serotypes identified within the past several years (Tehran and Pirazzini, 2018). BoNT/A, /B, /E, and /F are the etiological sources of most cases of endemic human botulism.…”

A comparison of biological activity of commercially available purified native botulinum neurotoxin serotypes A1 to F1 in vitro, ex vivo, and in vivo

“…BoNT products exert their effect through inhibition of neurotransmitter release, most notably of acetylcholine, at the neuromuscular junction . BoNTs are diverse proteins and are represented by at least seven serotypes and more than 40 subtypes, and recently new BoNT‐like proteins have been reported . Of the seven naturally occurring immunologically distinct BoNT serotypes (termed A to G) described so far, only A and B are currently used in the clinical practice.…”

Cervical Dystonia and Executive Function: A Pilot Magnetoencephalography Study

“…Botulinum toxins function by cleaving members of the soluble N -ethylmaleimide-sensitive-factor attachment receptor (SNARE) protein family, which are responsible for mediation of the fusion of synaptic vesicles with the neuronal presynaptic plasma membrane [ 11 ]. Proteolysis of these proteins therefore interrupts neurotransmission and leads to flaccid paralysis of the muscle.…”