Molecular mechanism and effects of clostridial neurotoxins

Abstract

The genus Clostridia, gram-positive anaerobic bacteria, produce two of the deadliest toxins known to mankind: Tetanus and botulinum. Toxicity of these molecules comes from their action on very specific substrates, SNARE proteins, in the neuronal cells. They cleave SNAREs, which are the crucial components of neuroexocytosis, causing inhibition of release of neurotransmitters at the synapses. Botulinum neurotoxin molecule has evolved itself to have high stability, specificity, and selectivity. It maneuvers and exploits itself in each step of intoxication and preserves its active structure to achieve an exquisite toxicity. The mechanisms of action and biological functions of clostridial neurotoxins still have several unresolved questions. Several unique characteristics of these neurotoxins attract scientists to understand the mysteries of neurotoxin molecules. Despite high toxicity, botulinum neurotoxin has a wide range of medicinal applications. In the last few decades, toxin transformed itself from life- threatening disease to a wonder drug. Therapeutic use of botulinum neurotoxin is based on three unique features: Specificity, potency, and duration of action. Active research is underway to transform botulinum neurotoxins into the most versatile and useful drugs for neuromuscular disorders, and as cosmeceuticals. This chapter summarizes current knowledge on its structure and mechanism of intoxication. It also describes basic understanding of the evolution of this molecule to achieve this extremely high biological activity in terms of toxicity or therapeutics. Understanding the true nature and function of its dynamic structure still remains a work in progress.