Introduction

Botulinum neurotoxins (BoNTs) are proteins derived from the bacterium Clostridium botulinum that have been formulated as drug products for clinical use. These biologics are typically injected into muscles where they act locally to inhibit the release of acetylcholine at the neuromuscular junction. Botulinum neurotoxins can also act on cholinergic autonomic terminals following injection into smooth muscle, where they inhibit contractions, or nearby glands, where they inhibit glandular secretions. Additionally, they can inhibit release of inflammatory peptides at pain endings.

Synthesis and structure

C. botulinum produces BoNTs as protein complexes that contain non-toxin hemagglutinin and non-hemagglutinin proteins in addition to the neurotoxin itself. The type and number of non-toxin proteins are determined by the strain of the bacteria, and these proteins form complexes with the neurotoxin that range in molecular weight from approximately 300 kDa to approximately 900 kDa (Sakaguchi et al., 1984). Seven different BoNTs serotypes are produced by different clostridial strains, A, B, C1, D, E, F and G. Only types A and B are commercially available; types C and F have been tried in humans on an experimental basis only.