Study of mechanism of action of Scorpion neurotoxins

Summary Scorpions are important representative of arthropods. They have been well adapted to the extremes of environmental conditions. Scorpions also play a vital role in ecological systems by maintaining balance between different populations in an ecosystem. Apart from their positive role scorpions are responsible for more than 1.2 million stings per year with almost 3000 deaths worldwide per year and thus posing serious threat to public health. Two families of scorpions i.e. Buthida and Hemiscorpiidae are dangerous for humans. Scorpion sting can result in mild effects of redness and pain to very severe and lethal effects which can result failure of multiple organs eventually leading to death. Scorpion venom is composed of many different components such as low molecular weight peptides, nucleotides, lipids and certain enzymes. The diverse detrimental effects of scorpion sting result due to presence of many different types of toxins (neurotoxin, cardiotoxin, nephrotoxin, hemolytic toxin) and different enzymes (phosphodiesterases, phospholipases and hyaluronidases) in their venom. Since scorpions have a long evolutionary history during this long time period scorpions have developed a series of venom peptides that display a diverse range of biological functions. The most widely studied components of scorpion venom are the ion channel-modulating toxins which have been studied and described in detail in literature. Antarease a new class of unique scorpion metalloproteases capable of cleaving SNARE proteins has been described only recently with no previous evidence on presence of such enzymes in scorpions. Up till now SNARE proteins have only been shown to be targets of clostridial neurotoxins. To investigate such a class of metalloproteases we have analyzed the action of different scorpion venoms both on recombinant SNARE proteins as well as in neuronal cell models. Conclusion: This study shows for the first time the presence of antarease like proteins in scorpion species: Buthus eupeus and Orthochirus scrobiculosus. Both of the scorpion species contain active components i.e. metalloproteases that are able to cleave SNARE proteins in a mechanism similar to antarease.