Secreted Phospholipases A(2) With Beta-Neurotoxic Activity

Natural toxins are a threat to health but have also turned out to be very useful. Among the most illustrative examples are the deadly botulinum toxins that are used today in numerous therapeutic applications. The essential condition for a toxin to be used as a medicament or a research tool is to understand about how it interferes with the victim's physiology. In this chapter, a group of snake venom toxins is described, the beta-neurotoxins, whose mechanism of action at the molecular level is still not completely understood, leaving their medical potential yet to be exploited. As explained, these molecules have evolved by a process of accelerated evolution from harmless digestive enzymes, the secreted phospholipases A(2), to potent toxins that block synaptic signaling in vertebrate skeletal muscles. To advance the insight into the molecular basis of action of beta-neurotoxins, the results of the most recent investigations have been examined critically. A draft picture of how beta-neurotoxins poison the nerve terminal is presented. Important details, including the identity of beta-neurotoxicity-linked receptors, pathways by which beta-neurotoxins cross plasma and mitochondrial membranes, and intracellular regulation of their enzymatic activity, are however still unknown. Unraveling these issues should provide considerable support for clarifying the functions and dysfunctions of mammalian secreted phospholipases A2 in the nervous system.