Title: Botulinum neurotoxins: from the gut to the nervous system

Authors: Chloé Connan; Michel R. Popoff

Addresses: Unité des Bactéries anaérobies et Toxines, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, cedex 15, France ' Unité des Bactéries anaérobies et Toxines, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, cedex 15, France

Abstract: Botulinum neurotoxins (BoNTs) are potent toxins, which block the neurotransmitter release at neuromuscular junctions and are responsible for a severe disease, the botulism. In the natural disease, BoNTs are the most frequently acquired by the oral route. BoNT associates to non-toxic proteins (ANTPs), which have a main role in toxin protection against acidic pH and proteases, especially in the gastrointestinal tract. BoNTs which transit through the digestive tract, have first to cross the epithelial barrier. BoNTs are able to undergo a receptor-mediated transcytosis, which delivers the whole and active toxin at the basolateral side of epithelial cells. ANTPs containing hemagglutinins have an additional role in altering the intercellular junctions and facilitating a toxin passage through the paracellular way. Then, BoNT disseminates locally and at distance via the blood/lymph circulation and possibly via a retrograde axonal transport to the target motoneuron endings, where the toxin uses an endocytic pathway permitting the release of the light chain into the cytosol and its subsequent proteolytic activity towards the SNARE proteins involved in the neurotransmitter exocytosis.

Keywords: Clostridium botulinum; botulinum neurotoxins; BoNT; intestines; intestinal barrier; nervous system; gut; neurotransmitter release; neuromuscular junctions; botulism.

DOI: 10.1504/TBJ.2015.078139

The Botulinum Journal, 2015 Vol.3 No.1, pp.55 - 78

Received: 08 May 2021
Accepted: 12 May 2021

Published online: 01 Aug 2016 *

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