Botulinum neurotoxin serotype A1 (BoNT/A1)

Botulinum neurotoxin serotype A1 (BoNT/A1) is a highly potent neurotoxin produced by the bacterium Clostridium botulinum. It is a 150 kDa dichain protein consisting of a 100 kDa heavy chain and a 50 kDa light chain linked by a disulfide bond. The heavy chain mediates high-affinity binding to presynaptic receptors (polysialogangliosides and SV2) on cholinergic neurons, facilitating its internalization. The light chain acts as a zinc-dependent endopeptidase that, upon entering the cytosol, specifically cleaves the SNARE protein SNAP-25. This action prevents the fusion of acetylcholine-containing vesicles with the presynaptic membrane, thereby blocking neurotransmission and causing localized muscle paralysis. While it is the causative agent of botulism, BoNT/A1 is widely used therapeutically in purified forms, such as OnabotulinumtoxinA, to treat conditions like cervical dystonia, chronic migraine, and spasticity, as well as for cosmetic applications. Notable safety concerns include the potential for the toxin to spread from the injection site, which can lead to life-threatening respiratory failure (FDA: Botox Label).

Other names

Botulinum toxin type ABoNT/ABontoxilysin-AClostridium botulinum neurotoxin type ABotoxOnabotulinumtoxinAAbobotulinumtoxinAIncobotulinumtoxinA

Botulinum neurotoxin serotype A1 is a zinc-dependent endopeptidase that specifically cleaves the Synaptosomal-Associated Protein of 25 kDa (SNAP-25) at the Gln197-Arg198 bond (UniProt: P10845). This cleavage prevents the assembly of the SNARE (Soluble NSF Attachment Protein Receptor) complex, which is required for the fusion of synaptic vesicles with the presynaptic membrane. Consequently, the release of the neurotransmitter acetylcholine is inhibited at the neuromuscular junction, leading to flaccid muscle paralysis (PMID: 28415162, 15172737).