Central Action of Botulinum Toxin Type A – Is It Possible?

Abstract

Botulinum toxin (BoTx) is a product of gram-positive anaerobic bacteria of the Clostridium genus. At present, seven serotypes (A to G) of BoTx have been identified. Each of them functions as a zinc-dependent endopeptidase that hydrolyzes peptide bonds within soluble N-ethylmaleimide-sensitive factor attaching protein receptors. BoTx affects proteins required for neurotransmitter release through presynaptic membranes. As a result, muscle weakness develops, or complete paralysis of the muscles occurs. These effects are not only limited to striated muscles but also may have impact on smooth muscles and secretory glands. The observation that BoTx can diffuse from the site of administration may indicate the possibility of direct or indirect influence of the toxin on the CNS. Consequently, the question arises: What is the mechanism of the central action of BoTx? Several mechanisms of such action have been proposed. However, recent findings showed that the most probable mechanism responsible for the central effects of BoTx action is its anterograde transport. In this review, we describe and discuss the most important aspects related to BoTx action on the CNS.