Scorpion toxins targeting Kv1.3 channels: insights into immunosuppression

Abstract

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.

Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection

“…Cytokines play a key role in amplifying the response/communication among cell types, building an efficient response against pathogens. Herein, TsV, F6, and F7 fractions were potent inducers of IL-12p70/TNF/IL-6 in MOs, which is consistent with previous studies demonstrating that TsV-stimulated MOs secrete IL-1/IL-6/TNF/IFN-γ ( Petricevich, 2002 ; Oliveira et al., 2019 ; Pimentel et al., 2021 ). Of great relevance, we demonstrated that TsV compounds induced the production of IL-12 and TNF by T. gondii -infected MOs, abolishing the capacity of the parasite to evade host immunity.…”

“…T. serrulatus Venom Against Toxoplasma consistent with previous studies demonstrating that TsVstimulated MOs secrete IL-1/IL-6/TNF/IFN-g (Petricevich, 2002;Oliveira et al, 2019;Pimentel et al, 2021). Of great relevance, we demonstrated that TsV compounds induced the production of IL-12 and TNF by T. gondii-infected MOs, abolishing the capacity of the parasite to evade host immunity.…”

“…TsV was described to stimulate MOs through a complex interaction involving membrane receptors (e.g., Toll-like receptor 2/4) ( Zoccal et al., 2014 ), ion channels (e.g., Na + , Ca + , and K + ) ( Lowry et al., 1998 ; Oliveira et al., 2019 ), and Mitogen-Activated Protein Kinases (MAPK) ( Pimentel et al., 2021 ) which culminate in the production of inflammatory mediators. Cytokines play a key role in amplifying the response/communication among cell types, building an efficient response against pathogens.…”

From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery

“…In particular, those inhibiting K v 1.3 currents are considered potential bioactive molecules to treat autoimmune diseases (Zhao et al, 2015). To the best of our knowledge, there are 81 scorpion toxins with positive results in inhibiting K v 1.3 (Oliveira et al, 2019). Nevertheless, only eight of them present in vivo assays (i.e.…”

Discovery of KV1.3 ion channel inhibitors: Medicinal chemistry approaches and challenges

“…Many peptides that act on K V 1.3 with excellent potencies have been isolated and described 6,127 . A frequently occurring pitfall, however, is insufficient selectivity for K V 1.3 over other K V channels, and especially over K V 1.1, because of its high homology to K V 1.3 (65%–70%) 73 .…”