Emerging Opportunities for Serotypes of Botulinum Neurotoxins

Abstract

Background: Two decades ago, botulinum neurotoxin (BoNT) type A was introduced to the commercial market. Subsequently, the toxin was approved by the FDA to address several neurological syndromes, involving muscle, nerve, and gland hyperactivity. These syndromes have typically been associated with abnormalities in cholinergic transmission. Despite the multiplicity of botulinal serotypes (designated as types A through G), therapeutic preparations are currently only available for BoNT types A and B. However, other BoNT serotypes are under study for possible clinical use and new clinical indications; Objective: To review the current research on botulinum neurotoxin serotypes A-G, and to analyze potential applications within basic science and clinical settings; Conclusions: The increasing understanding of botulinal neurotoxin pathophysiology, including the neurotoxin’s effects on specific neuronal populations, will help us in tailoring treatments for specific diagnoses, symptoms and patients. Scientists and clinicians should be aware of the full range of available data involving neurotoxin subtypes A-G.

The Safety and efficacy of botulinum toxin type A injection for postoperative scar prevention: A systematic review and meta‐analysis

“…The mechanical signals generated by tension on both sides of the wound can affect the movement and contraction of fibroblasts, the expression of Type I collagen, and the transformation from fibroblasts to myofibroblasts . However, the N‐terminal of BTXA light chain has the activity of zinc metalloproteinase, which can cut the synaptosomal‐associated protein of 25 kDa (SNAP‐25) and prevent the release of acetylcholine into the synaptic cleft, thus causing “chemo‐denervation,” reducing the tension on both sides of the wound and affecting the scar morphology . In addition, some evidences suggest that BTXA may affect scar formation by reducing fibroblast proliferation, reducing TGF‐β expression, and altering collagen deposition and remodeling processes .…”

“…3 and prevent the release of acetylcholine into the synaptic cleft, thus causing "chemo-denervation," reducing the tension on both sides of the wound and affecting the scar morphology. 25,26 In addition, some evidences suggest that BTXA may affect scar formation by reducing fibroblast proliferation, reducing TGF-β expression, and altering collagen deposition and remodeling processes. 27 further reduce the content of TGF-β1 28 and its downstream regulator connective tissue growth factor (CTGF).…”

The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly molecule to treat disease in the skin and beyond

“…Molecular mechanisms of botulinum neurotoxins (Bo NT ) action (modified from Peng Chen et al .) . Bo NT subtypes inhibit the release of acetylcholine ( AC h) from the synaptic vesicle of the nerve ending into the synaptic cleft, resulting in ‘chemical denervation’.…”

Botulinum Toxin as a Pain Killer: Players and Actions in Antinociception

“…The other 50 kDa of the N -terminal domain (H N ) is the translocation domain, which interacts with the active site of the LC, which is a metalloprotease. The seven serotypes of BoNTs, termed A–G, bind to and enter synaptic terminals and cleave one of the soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, vesicle-associated membrane protein (VAMP), synaptosomal-associated protein 25 (SNAP25), or syntaxin [ 3 ]. These SNARE proteins mediate synaptic vesicle fusion; therefore, BoNTs inhibit the exocytosis of synaptic vesicles containing neurotransmitters [ 4 ].…”