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. 2024 Jun 10;16(6):266. doi: 10.3390/toxins16060266

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© 2024 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Mechanism of action of BoNT/A. The top panel shows fusion of cholinergic synaptic vesicles with the motor nerve terminal membrane in the absence of BoNT/A. Vesicles bud off the early endosome and are loaded with acetylcholine (1). The vesicle approaches the nerve terminal membrane (2), where the SNARE proteins in the vesicle membrane (VAMP; red) and neuronal membrane (syntaxin—blue; SNAP-25—gold) assist with vesicle docking and fusion (3). Acetylcholine is released into the synaptic cleft (4) where it binds to cholinergic receptors on motor neurons (5). The bottom panel shows the mechanism by which BoNT/A inhibits cholinergic neurotransmission. BoNT/A binds to gangliosides and the protein SV2 in the nerve terminal membrane (1). BoNT/A is then internalized into the neuron via receptor-mediated endocytosis (2). The BoNT/A heavy chain translocates the light chain of the protein across the synaptic vesicle membrane into the cytoplasm (3–5), where the light chain functions as a zinc-dependent protease, cleaving SNAP-25 and preventing vesicle fusion and hence acetylcholine release (6).

Mechanism of action of BoNT/A. The top panel shows fusion of cholinergic synaptic vesicles with the motor nerve terminal membrane in the absence of BoNT/A. Vesicles bud off the early endosome and are loaded with acetylcholine (1). The vesicle approaches the nerve terminal membrane (2), where the SNARE proteins in the vesicle membrane (VAMP; red) and neuronal membrane (syntaxin—blue; SNAP-25—gold) assist with vesicle docking and fusion (3). Acetylcholine is released into the synaptic cleft (4) where it binds to cholinergic receptors on motor neurons (5). The bottom panel shows the mechanism by which BoNT/A inhibits cholinergic neurotransmission. BoNT/A binds to gangliosides and the protein SV2 in the nerve terminal membrane (1). BoNT/A is then internalized into the neuron via receptor-mediated endocytosis (2). The BoNT/A heavy chain translocates the light chain of the protein across the synaptic vesicle membrane into the cytoplasm (3–5), where the light chain functions as a zinc-dependent protease, cleaving SNAP-25 and preventing vesicle fusion and hence acetylcholine release (6).