What is the mechanism of action in botulinum toxin (BoNT)?

Updated: Jul 13, 2018
  • Author: Divakara Kedlaya, MBBS; Chief Editor: Elizabeth A Moberg-Wolff, MD  more...
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Answer

Answer

Botulinum toxin acts by binding presynaptically to high-affinity recognition sites on the cholinergic nerve terminals and decreasing the release of acetylcholine, causing a neuromuscular blocking effect. This mechanism laid the foundation for the development of the toxin as a therapeutic tool.

Recovery occurs through proximal axonal sprouting and muscle re-innervation by formation of a new neuromuscular junction. De Paiva and colleagues suggest that eventually the original neuromuscular junction regenerates. [3]

  • BoNT-A and BoNT-E cleave synaptosome-associated protein (SNAP-25), a presynaptic membrane protein required for fusion of neurotransmitter-containing vesicles. [4]

  • BoNT-B, BoNT-D, and BoNT-F cleave a vesicle-associated membrane protein (VAMP), also known as synaptobrevin.

  • BoNT-C acts by cleaving syntaxin, a target membrane protein.

Table 1. Botulinum Toxin Types, Target Sites, Discoverers, and Year Discovered (Open Table in a new window)

Type

Target

Discoverer

Year

A

SNAP-25

Landman

1904

B

VAMP

Ermengem

1897

C1

Syntaxin

Bengston and Seldon

1922

D

VAMP

Robinson

1929

E

SNAP-25

Gunnison

1936

F

VAMP

Moller and Scheibel

1960

G

VAMP

Gimenez and Ciccarelli

1970


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