Editorial : Special Issue on "Toxins: New targets and new functions".

Evelyne Benoit (1) , Julien Barbier (2) , Michel R Popoff (3) , Grazyna Faure (4) , Jordi Molgó (1) , Denis Servent (2)

1 NeuroPSI - Institut des Neurosciences Paris-Saclay
2 SIMoS - Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO)
3 Bactéries anaérobies et Toxines
4 Récepteurs Canaux - Channel Receptors

The first session was devoted to toxins acting on the nervous system. In this session Emmanuel BOURINET (Montpellier, France) reported that the T-type calcium channel Cav3.2 is a key regulator of sensory functions in touch/pain pathophysiology, with pharmacological relevance to relieve allodynia and hyperalgesia. Thus, the large potential of venom neurotoxins offers new venues for discovering subtype specific T-type channel blockers with high analgesic potential. Eugene GRISHIN (Moscow, Russia) showed that the natural peptides (Purotoxin-1 and-2), isolated from the spider Alopecosa marikovskyi, possess selective inhibitory activity on purinergic P2X3 receptors. It seems likely that when the P2X3 receptors are desensitized, purotoxins bind to them and inhibit receptor activity. Purotoxin-1 demonstrated potent anti-nociceptive properties in animal models of inflammatory pain, since P2X3 receptors are expressed in mammalian sensory neurons and likely play a substantial role in pain perception. Detailed information on inactive and active peptides, identified in the venom of the sea anemone Urticina grebelnyi, some of which selectively inhibited the ASIC3 channel, and significantly reversed inflammatory and acid-induced pain in vivo, were presented (see the original article by OSMAKOV et al. in this issue). Using site directed mutagenesis, the influence of individual amino acid substitution on the peptides was studied in order to determine the essential structural factor necessary for inhibiting ASIC3 activity. Also, short mutant peptides (22 amino acids), truncated at both N-and C-termini, were reported to exhibit a significant anti-inflammatory effect in vivo. Yara CURY (Sao Paulo, Brazil) reviewed the antinociceptive effect of crotalphine, a peptide isolated from the South American rattlesnake Crotalus durissus terrificus venom, and the peripheral interactions between the opioid and cannabinoid systems in pain control. Grazyna FAURE (Paris, France) presented new information on the actions of crotoxin, a potent β-neurotoxin from the venom of the rattlesnake C. d. terrificus, which exhibits PLA2 activity and neurotoxicity. Using surface plasmon resonance and other biochemical and biophysical techniques, two novel specific targets of the rattlesnake PLA2 were discovered including the cystic fibrosis transmembrane conductance regulator (CFTR) and the bacterial pentameric proton-gated ion channel (GLIC). Thus, GLIC was identified as a new protein target for PLA2 and PLA2 as a new ligand/regulator of GLIC proton-gated ion channel activity (see the original article by OSTROWSKI et al. in this issue). In addition, it was shown that the PLA2-GLIC interaction involves the extracellular domain of GLIC. Christian LEGROS (Angers, France) reported the suitability of novel voltage-sensor probes to challenge the discovery of new inhibitors and modulators of voltage-gated sodium channels.

Domaines: Neurobiologie; Psychologie et comportements; Sciences cognitives

Evelyne Benoit, Julien Barbier, Michel R Popoff, Grazyna Faure, Jordi Molgó, et al.. Editorial : Special Issue on "Toxins: New targets and new functions".. Toxicon, 2016, 116, pp.1-3. ⟨10.1016/j.toxicon.2016.03.012⟩. ⟨hal-01306142⟩