Cellular Mechanisms of Action of Snake Phospholipase A2 Toxins

Snake venoms contain a large amount of toxins endowed with phospholipase A2 (PLA2) activity. Despite an overall conserved structure, snake PLA2s display a variety of pharmacological activities that are the result of different cell targets and mode of actions. Here follows an overview of the present knowledge on the mechanism of action of the two main classes of snake PLA2s, myotoxins and neurotoxins, derived from in vivo, ex vivo, and in vitro models, along with a comparison with mammalian secreted PLA2 (sPLA2) homologues. In spite of many qualified efforts, several aspects of snake envenomation are still undefined, including the identification of specific receptors on nerve and muscle membranes. Further studies are required to elucidate the unclear molecular steps of snakebite intoxication that might contribute to shed light also on the mode of action of mammalian PLA2 counterparts. There is a high degree of homology in terms of primary structure between snake and mammalian sPLA2s, suggesting that snake PLA2 receptors might be also candidates for mammalian sPLA2s; this topic is of high relevance, in the light of the emerging involvement of mammalian sPLA2s in many human disorders.