Botulinum Toxin at the Neuromuscular Junction: Mechanism of Paralysis

Botulinum neurotoxin (BoNT) blocks acetylcholine (ACh) release at the neuromuscular junction (NMJ), causing flaccid paralysis.

NMJ Structure

• Motor neuron terminal (presynaptic)
• Synaptic cleft
• Muscle fiber endplate (postsynaptic, ACh receptors)

Mechanism

1. BoNT binds presynaptic membrane (SV2 receptor)
2. Internalized via endocytosis
3. Light chain (zinc protease) cleaves SNARE proteins (SNAP-25, synaptobrevin, syntaxin)
4. Vesicle fusion blocked → no ACh release
5. No endplate potential → no muscle contraction

Clinical Effects

• Onset: 24–72 hours
• Peak: 1–2 weeks
• Duration: 3–6 months (sprouting of new terminals restores function)
• Dose-dependent, reversible

Therapeutic Uses

• Focal dystonias, spasticity, chronic migraine, hyperhidrosis, blepharospasm, cosmetic (glabellar lines)