New and emerging indications of botulinum toxin therapy

Botulinum neurotoxin (BoNT) is composed of the heavy chain with the receptor-binding site and the translocation domain and the light chain with endopeptidase activity that cleaves the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex, an essential molecule for membrane fusion. Its extraordinarily high toxicity depends on the affinity of the receptor-binding site to the receptor located inside the synaptosome. The membrane fusion mechanism is important not only in neurotransmitter release at the nerve terminals but also in the expression of pain receptors on the cell surface. Based on these mechanisms, BoNT is increasingly used for varieties of conditions including cosmetic uses, muscle hyperactivity, hyperhydrosis, pain, overactive bladder and epilepsy. It will become a major arm of neuromodulating treatments for neurological diseases. A part of this toxin, such as the heavy chain, may become a novel drug-delivery system for neurodegenerative diseases.