Multi-scale evaluation of spider toxins as potential anti-nociceptive agents: example of cyriotoxin-1a - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2021

Multi-scale evaluation of spider toxins as potential anti-nociceptive agents: example of cyriotoxin-1a

Résumé

Our expertise is the identification and structural and functional characterization of original natural toxins targeting receptors and ion channels, and which may have applications in human health. In this context, and in collaboration with the Institut du Thorax, Smartox Biotechnology and Sanofi R & D, we are interested in the multi-scale evaluation (from the cell in vitro to the organism in vivo) of spider toxins as potential anti-nociceptive agents, as illustrated by the example of Cyriotoxin-1a (CyrTx-1a). NaV1.7 channel subtype is highly expressed in dorsal root ganglia (DRG) of the sensory nervous system and plays a central role in the pain signaling process. We investigated a library prepared from original venoms of 117 different animals to identify new selective inhibitors of this target. We used high-throughput screening of the venom library, using automated patch-clamp experiments on human voltagegated sodium channel subtypes, and then in vitro and in vivo electrophysiological experiments to characterize the active peptides that have been purified, sequenced and chemically synthesized. Analgesic effects were evaluated in mice in vivo. We identified and further characterized CyrTx-1a, a novel peptide isolated from Cyriopagopus schioedtei spider venom. This 33 amino acids toxin belongs to the inhibitor cystine knot structural family and inhibits hNaV1.1-1.3 and 1.6-1.7 in the low nanomolar range, compared to the micromolar range for hNaV1.4-1.5 and 1.8. CyrTx-1a was 920 times more efficient at inhibiting tetrodotoxin (TTX)-sensitive than TTX-resistant sodium currents recorded from adult mouse DRG neurons in vitro, and approximately 170 times less efficient than huwentoxin-IV at altering mouse skeletal neuromuscular excitability in vivo. CyrTx-1a exhibited an analgesic effect in mice by significantly increasing reaction time in the hot-plate assay.
Fichier principal
Vignette du fichier
2021-SFET-RT27_Virtuel-211209-10_Poster-211108EB.pdf (640.64 Ko) Télécharger le fichier
RT27-BENOIT-Abstract.pdf (145.73 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-04471737 , version 1 (21-02-2024)

Identifiants

  • HAL Id : hal-04471737 , version 1

Citer

Evelyne Benoit, Michel de Waard, Rémy Béroud, Michel Partiseti, Denis Servent. Multi-scale evaluation of spider toxins as potential anti-nociceptive agents: example of cyriotoxin-1a. RT27 – 27th Meeting of the French Society of Toxinology – Toxins: Mr Hyde or Dr Jekyll?, Dec 2021, Paris (Virtual), France. ⟨hal-04471737⟩
19 Consultations
5 Téléchargements

Partager

Gmail Facebook X LinkedIn More