THE NON-NEURONAL AND NON-MUSCULAR EFFECTS OF BOTULINUM TOXIN: A Graceful Opportunity for a Deadly Molecule to Treat a Human Disease in the Skin and Beyond

Abstract

There is growing evidence that botulinum neurotoxins (BoNTs) exhibit biological effects on various human cell types with a host of associated clinical implications. The BoNT receptors and intracellular targets are not unique for neurotransmission. They have been found in both neuronal and non-neuronal cells, but there are differences in the way BoNT binds to, and acts on neuronal vs. non-neuronal cells. The non-neuronal cells expressing one or more BoNT/A-binding proteins and/or cleavage target SNAP-25 include epidermal keratinocytes, mesenchymal stem cells from subcutaneous adipose, nasal mucosal cells, urothelial cells, intestinal epithelial cells, neutrophils, macrophages, and prostate, breast and alveolar epithelial cells, BoNT/A can also elicit specific biological effects in dermal fibroblasts, sebocytes and vascular endothelial cells. The reported non-traditional applications of BoNT in dermatologic conditions include hyperhidrosis, Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenita, multiple eccrine hydrocystomas, eccrine angiomatous hamartoma, eccrine sweat gland nevi, congenital eccrine nevus, Raynaud phenomenon and cutaneous leiomyomas. Experimental studies demonstrated BoNT/A ability to protect skin flaps, facilitate wound healing, decrease thicknesses of hypertrophic scars, produce an anti-aging effect, and improve a mouse model of psoriasiform dermatitis. Furthermore, experimental studies also have revealed extracutaneous effects of BoNT arising from its anti-inflammatory and anti-cancer properties. Therefore, it is clear that BoNTs have a much wider zone of influence than originally understood, and that these ubiquitous events are based on individual cellular responses to the cholinergic impacts of BoNTs, which represents fertile grounds for future studies that are highly likely to result in impactful discoveries.

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