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

摘要

Summary There is growing evidence that botulinum neurotoxins (BoNTs) exhibit biological effects on various human cell types with a host of associated clinical implications. This review aims to provide an update on the nonneuronal and nonmuscular effects of botulinum toxin. We critically analysed recent reports on the structure and function of cellular signalling systems subserving biological effects of BoNT s. The BoNT receptors and intracellular targets are not unique for neurotransmission. They have been found in both neuronal and nonneuronal cells, but there are differences in how BoNT binds to, and acts on, neuronal vs. nonneuronal cells. The nonneuronal cells that express one or more BoNT /Abinding proteins, and/or cleavage target synaptosomalassociated protein 25, include: epidermal keratinocytes; mesenchymal stem cells from subcutaneous adipose; nasal mucosal cells; urothelial cells; intestinal, prostate and alveolar epithelial cells; breast cell lines; neutrophils; and macrophages. Serotype BoNT /A can also elicit specific biological effects in dermal fibroblasts, sebocytes and vascular endothelial cells. Nontraditional applications of BoNT have been reported for the treatment of the following dermatological conditions: hyperhidrosis, HaileyHailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenita, multiple eccrine hydrocystomas, eccrine angiomatous hamartoma, eccrine sweat gland naevi, congenital eccrine naevus, Raynaud phenomenon and cutaneous leiomyomas. Experimental studies have demonstrated the ability of BoNT /A to protect skin flaps, facilitate wound healing, decrease thickness of hypertrophic scars, produce an antiageing effect, improve a mouse model of psoriasiform dermatitis, and have also revealed extracutaneous effects of BoNT arising from its antiinflammatory and anticancer properties. BoNT s have a much wider range of applications than originally understood, and the individual cellular responses to the cholinergic impacts of BoNT s could provide fertile ground for future studies.