Botulinum Neurotoxins: History, Mechanism, and Applications. A Narrative Review.

Area of Science:

• Neuroscience
• Microbiology
• Pharmacology

Background:

• Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and cause neuroparalysis by targeting presynaptic cholinergic nerve terminals.
• BoNTs consist of heavy and light chains; the light chain is a zinc-dependent metalloprotease that cleaves SNARE proteins, inhibiting acetylcholine release and causing flaccid paralysis.
• Botulism intoxication, including foodborne, wound, and infant forms, is associated with heat-resistant bacterial endospores.

Purpose of the Study:

• To elucidate the mechanism of action of BoNTs on neuronal communication.
• To explore the differences in origin, mechanism, structure, and interactions among BoNT serotypes.
• To highlight the clinical application and optimization of BoNTs as therapeutic agents.

Main Methods:

• Review of the molecular structure and function of BoNTs, including heavy and light chain activities.
• Analysis of the mechanism of SNARE protein cleavage and its effect on synaptic vesicle fusion.
• Examination of the clinical applications and molecular engineering of BoNT/A and BoNT/B serotypes.

Main Results:

• BoNTs specifically target presynaptic nerve terminals, cleave SNARE proteins, and inhibit acetylcholine release, leading to flaccid paralysis.
• Different BoNT serotypes exhibit variations in their origin, mechanism of action, structure, and interactions.
• Low doses of BoNT/A and BoNT/B have been clinically harnessed for therapeutic purposes, demonstrating selective neuronal silencing.

Conclusions:

• BoNTs are potent neurotoxins that disrupt neuronal communication through specific molecular mechanisms.
• Molecular engineering has transformed BoNTs into safe and targeted therapeutic agents for various medical conditions.
• The selective neuronal silencing properties of BoNTs are replicated in their optimized pharmacological formulations.