The underlying mechanism of scorpion venom peptide BmK AS in reducing epilepsy seizures: mediated through dual modulation of Nav1.6 and the inflammasome pathway

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  The underlying mechanism of scorpion venom peptide BmK AS in reducing epilepsy seizures: mediated through dual modulation of Nav1.6 and the inflammasome pathway Abstract Introduction:  Voltage-gated sodium channel (VGSC) dysregulation, particularly of the Nav1.6 subtype, is a core mechanism underlying epileptogenesis and its associated neuropsychiatric comorbidities. The scorpion venom peptide BmK AS has demonstrated anticonvulsant potential, but its efficacy in chronic epilepsy and the precise mechanisms of action remain undefined. Methods:  Here, we show that BmK AS exerts robust anti-epileptic and neuroprotective effects through converging mechanisms. In a kainic acid-induced mouse model, BmK AS treatment reduced mortality and seizure parameters. Electrophysiological studies assessed BmK AS modulation of VGSC subtypes. The functional relevance of Nav1.6 targeting was confirmed by the loss of BmK AS’s anti-seizure efficacy upon its pharmacological blockade in a PTZ-in...

Venom Diversity: Exploring the inter- and intra-specific variability of Androctonus scorpion venoms

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Venom Diversity: Exploring the inter- and intra-specific variability of Androctonus scorpion venoms


Abstract:

From its lethal sting to its medicinal potential, scorpion venom is a paradoxical elixir of nature. This venom contains a variety of molecules, including enzymes, molecules involved in allergic reactions, and, most notably, neurotoxins that exert a potent pharmacological activity on the membrane of ion channels of excitable cells. In this study, we conducted an exhaustive analysis of the venoms derived from Moroccan scorpions belonging to the Androctonus genera. Using electrospray mass spectrometry coupled with high-performance liquid chromatography (HPLC), we aimed to provide detailed information regarding the composition and molecular nature of these venoms. We initially fractionated the venoms using HPLC, and the fractions were subsequently analyzed via mass spectrometry to establish peptide maps and fingerprints for each venom. We obtained a wide range of molecular weights, varying between 236 and 622, depending on factors such as species, genus, geographical location, age, sex, and diet. Our analysis revealed that the molecular masses of the venoms were predominantly found between 2000 and 4000 Da and corresponded mainly to short toxins that blocked the K+ channels. Larger molecular weights exceeding 4000 Da were identified as long toxins modulating the Na+ channels. Moreover, we discovered other peptides below 2000 Da that were previously unknown. Our observations also indicated that the venom of the Androctonus genera contained higher quantities of masses corresponding to both long and short toxins. This study provides valuable insight into the complex composition of scorpion venoms and underscores the significance of understanding their composition in the development of novel therapeutic approaches.


HILAL, I.; KHOURCHA, S.; SAFI, A.; HMYENE, A.; STOCKLIN, R.; OUKKACHE, N. Venom Diversity: Exploring the inter- and intra-specific variability of Androctonus scorpion venoms., in Proceedings of the 2nd International Electronic Conference on Toxins, 14–28 July 2023, MDPI: Basel, Switzerland, doi:10.3390/IECT2023-14797