Abstract
Scorpions are fascinating creatures which became residents of the planet well before human beings dwelled on Earth. Scorpions are always considered as a figure of fear, causing notable pain or mortality throughout the world. Their venoms are cocktails of bioactive molecules, called toxins, which are responsible for their toxicity. Fortunately, medical researchers have turned the life-threatening toxins into life-saving therapeutics. From Song Dynasty in ancient China, scorpions and their venoms have been applied in traditional medicine for treating neurological disorders, such as pain, stroke, and epilepsy. Neurotoxins purified from Chinese scorpion Buthus Martensii Karsch (BmK) are considered as the main active ingredients, which act on membrane ion channels. Long-chain toxins of BmK, composed of 58–76 amino acids, could specifically recognize voltage-gated sodium channels (VGSCs). Short-chain BmK toxins, containing 28–40 amino acids, are found to modulate the potassium or chloride channels. These components draw attention as useful scaffolds for drug-design in order to tackle the emerging global medical threats. In this chapter, we aim to summarize the most promising candidates that have been isolated from BmK venoms for drug development.
Highlights
Recent advances underlying medical studies have illuminated that several neurological disorders such as epilepsy, chronic pain, multiple sclerosis, stroke, brain tumor etc. are induced by dysfunction of membrane ion channels [1–3]
The long-chain scorpion toxins composed of 58–76 amino acid residues mainly act on voltage-gated sodium channels (VGSCs), while the short-chain scorpion toxins containing 28–40 amino acid residues generally target K+ or Cl− channels [27] (Figure 1B)
Based on their physiological effects on VGSC gating and binding properties, the long-chain toxins can be further classified into two categories: α-toxins, such as Buthus Martensii Karsch (BmK) I, a 64-residue α-like toxin isolated from BmK [2], and BmK αIV, a novel cloned 68-residue polypeptide, binding to neurotoxin receptor site 3 of the VGSC, with inhibitory effects on the fast inactivation of VGSCs (Figure 2). β-toxins, which bind to receptor site 4 such as BmK IT2 as well as BmK anti-epilepsy peptide (BmK AEP), two 64-residue inhibitory β-toxins [28], and BmK AS, a 66-residue β-like toxin, could shift the threshold of VGSCs activation to more negative membrane potentials [29–32] (Figure 2)
Summary
Recent advances underlying medical studies have illuminated that several neurological disorders such as epilepsy, chronic pain, multiple sclerosis, stroke, brain tumor etc. are induced by dysfunction of membrane ion channels [1–3]. The long-chain scorpion toxins composed of 58–76 amino acid residues mainly act on voltage-gated sodium channels (VGSCs), while the short-chain scorpion toxins containing 28–40 amino acid residues generally target K+ or Cl− channels [27] (Figure 1B). Based on their physiological effects on VGSC gating and binding properties, the long-chain toxins can be further classified into two categories: α-toxins, such as BmK I, a 64-residue α-like toxin isolated from BmK [2], and BmK αIV, a novel cloned 68-residue polypeptide, binding to neurotoxin receptor site 3 of the VGSC, with inhibitory effects on the fast inactivation of VGSCs (Figure 2). We aim to describe the most promising candidates for drug development that have been isolated from BmK venoms, with categorization according to their biological activity
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