Scorpion toxins targeting Kv1 3 channels: insights into immunosuppression

Scorpion venoms are natural sources of molecules that have, in addition to their toxic function, potential therapeutic applications. In this source the neurotoxins can be found especially those that act on potassium channels. Potassium channels are responsible for maintaining the membrane potential in the excitable cells, especially the voltage-dependent potassium channels (Kv), including Kv1.3 channels. These channels (Kv1.3) are expressed by various types of tissues and cells, being part of several physiological processes. However, the major studies of Kv1.3 are performed on T cells due its importance on autoimmune diseases. Scorpion toxins capable of acting on potassium channels (KTx), mainly on Kv1.3 channels, have gained a prominent role for their possible ability to control inflammatory autoimmune diseases. Some of these toxins have already left bench trials and are being evaluated in clinical trials, presenting great therapeutic potential. Thus, scorpion toxins are important natural molecules that should not be overlooked in the treatment of autoimmune and other diseases.(AU)

Effects of Brazilian scorpion venoms on the central nervous system

In Brazil, the scorpion species responsible for most severe incidents belong to the Tityus genus and, among this group, T. serrulatus, T. bahiensis, T. stigmurus and T. obscurus are the most dangerous ones. Other species such as T. metuendus, T. silvestres, T. brazilae, T. confluens, T. costatus, T. fasciolatus and T. neglectus are also found in the country, but the incidence and severity of accidents caused by them are lower. The main effects caused by scorpion venoms - such as myocardial damage, cardiac arrhythmias, pulmonary edema and shock - are mainly due to the release of mediators from the autonomic nervous system. On the other hand, some evidence show the participation of the central nervous system and inflammatory response in the process. The participation of the central nervous system in envenoming has always been questioned. Some authors claim that the central effects would be a consequence of peripheral stimulation and would be the result, not the cause, of the envenoming process. Because, they say, at least in adult individuals, the venom would be unable to cross the blood-brain barrier. In contrast, there is some evidence showing the direct participation of the central nervous system in the envenoming process. This review summarizes the major findings on the effects of Brazilian scorpion venoms on the central nervous system, both clinically and experimentally. Most of the studies have been performed with T. serrulatus and T. bahiensis. Little information is available regarding the other Brazilian Tityus species.(AU)

Scorpions from the primeval subgenus Archaeotityus produce putative homologs of Tityus serrulatus toxins active on voltage-gated sodium channels

It has been proposed that the subgenus Archaeotityus comprises the most ancient species group within the medically important scorpion genus Tityus. cDNA encoding sodium-channel active toxins from the type species of this subgenus, Tityus clathratus (central Venezuela), have been isolated and sequenced. Two cDNAs were retrieved that encoded 61 amino acid-long putative neurotoxins named Tcl1 and Tcl2. Sequence identity was highest (87%) when both were compared with -toxin Ts1 from the Brazilian scorpion Tityus serrulatus and its homologs from T. bahiensis, T. stigmurus, and T. costatus. A Bayesian analysis indicated statistical support for the grouping of T. clathratus Tcl1 and Tcl2 with Brazilian gamma-like -toxins, reinforcing previous phylogenetic studies which suggested an evolutionary relationship between the subgenus Archaeotityus and scorpion species inhabiting southeast South America belonging to the subgenus Tityus.