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This 26th edition of the annual Meeting on Toxinology (RT26) of the SFET (http://sfet.asso.fr/international) was held at the Institut Pasteur of Paris on 4–5 December 2019
Pascale Marchot; Sylvie Diochot; Michel R. Popoff; Evelyne Benoit. Report from the 26th Meeting on Toxinology, “Bioengineering of Toxins”, Organized by the French Society of Toxinology (SFET) and Held in Paris, France, 4–5 December 2019. Toxins 2020, 12, 31 .
AMA StylePascale Marchot, Sylvie Diochot, Michel R. Popoff, Evelyne Benoit. Report from the 26th Meeting on Toxinology, “Bioengineering of Toxins”, Organized by the French Society of Toxinology (SFET) and Held in Paris, France, 4–5 December 2019. Toxins. 2020; 12 (1):31.
Chicago/Turabian StylePascale Marchot; Sylvie Diochot; Michel R. Popoff; Evelyne Benoit. 2020. "Report from the 26th Meeting on Toxinology, “Bioengineering of Toxins”, Organized by the French Society of Toxinology (SFET) and Held in Paris, France, 4–5 December 2019." Toxins 12, no. 1: 31.
Phlotoxin-1 (PhlTx1) is a peptide previously identified in tarantula venom (Phlogius species) that belongs to the inhibitory cysteine-knot (ICK) toxin family. Like many ICK-based spider toxins, the synthesis of PhlTx1 appears particularly challenging, mostly for obtaining appropriate folding and concomitant suitable disulfide bridge formation. Herein, we describe a procedure for the chemical synthesis and the directed sequential disulfide bridge formation of PhlTx1 that allows for a straightforward production of this challenging peptide. We also performed extensive functional testing of PhlTx1 on 31 ion channel types and identified the voltage-gated sodium (Nav) channel Nav1.7 as the main target of this toxin. Moreover, we compared PhlTx1 activity to 10 other spider toxin activities on an automated patch-clamp system with Chinese Hamster Ovary (CHO) cells expressing human Nav1.7. Performing these analyses in reproducible conditions allowed for classification according to the potency of the best natural Nav1.7 peptide blockers. Finally, subsequent in vivo testing revealed that intrathecal injection of PhlTx1 reduces the response of mice to formalin in both the acute pain and inflammation phase without signs of neurotoxicity. PhlTx1 is thus an interesting toxin to investigate Nav1.7 involvement in cellular excitability and pain.
Sébastien Nicolas; Claude Zoukimian; Frank Bosmans; Jérôme Montnach; Sylvie Diochot; Eva Cuypers; Stephan De Waard; Rémy Béroud; Dietrich Mebs; David Craik; Didier Boturyn; Michel Lazdunski; Jan Tytgat; Michel De Waard. Chemical Synthesis, Proper Folding, Nav Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1. Toxins 2019, 11, 367 .
AMA StyleSébastien Nicolas, Claude Zoukimian, Frank Bosmans, Jérôme Montnach, Sylvie Diochot, Eva Cuypers, Stephan De Waard, Rémy Béroud, Dietrich Mebs, David Craik, Didier Boturyn, Michel Lazdunski, Jan Tytgat, Michel De Waard. Chemical Synthesis, Proper Folding, Nav Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1. Toxins. 2019; 11 (6):367.
Chicago/Turabian StyleSébastien Nicolas; Claude Zoukimian; Frank Bosmans; Jérôme Montnach; Sylvie Diochot; Eva Cuypers; Stephan De Waard; Rémy Béroud; Dietrich Mebs; David Craik; Didier Boturyn; Michel Lazdunski; Jan Tytgat; Michel De Waard. 2019. "Chemical Synthesis, Proper Folding, Nav Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1." Toxins 11, no. 6: 367.
Background and purpose Acid‐Sensing Ion Channels (ASICs) are neuronal proton sensors emerging as potential therapeutic targets in pain of the orofacial region. Amiloride, a non‐specific ASIC blocker, has been shown to exert beneficial effects in animal models of migraine and in patients. We explored the involvement of the ASIC1‐subtype in cutaneous allodynia, a hallmark of migraine affecting cephalic and extra‐cephalic regions in about 70% of migrainers. Experimental approach We investigated the effects on cephalic and extra‐cephalic mechanical sensitivity of systemic injections of amiloride and mambalgin‐1, a specific inhibitor of ASIC1a‐ and ASIC1b‐containing channels, in a rodent model of acute and chronic migraine induced by intraperitoneal injections of isosorbide dinitrate. Key results Intravenous injection of these inhibitors reversed cephalic and extra‐cephalic acute cutaneous mechanical allodynia in rats, a single injection inducing a delay in the subsequent establishment of chronic allodynia. Mambalgin‐1 or amiloride also reversed established chronic allodynia. The anti‐allodynic effect of mambalgin‐1 was not altered in ASIC1a‐knock‐out mice, showing no contribution of the ASIC1a subtype in the effect.. Mambalgin‐1 anti‐allodynic effects are comparable to the ones of the anti‐migraine drug sumatriptan and of the preventive drug topiramate on acute and chronic allodynia, respectively. A single daily injection of mambalgin‐1 also had a significant preventive effect on allodynia chronification. Conclusions and Implications These pharmacological data support the involvement of peripheral ASIC1‐containing channels in migraine cutaneous allodynia as well as in its chronification. They highlight the therapeutic potential of ASIC1 inhibitors in migraine for both acute and prophylactic treatment.
Clément Verkest; Emilie Piquet; Sylvie Diochot; Mélodie Dauvois; Michel Lanteri-Minet; Eric Lingueglia; Anne Baron. Effects of systemic inhibitors of acid-sensing ion channels 1 (ASIC1) against acute and chronic mechanical allodynia in a rodent model of migraine. British Journal of Pharmacology 2018, 175, 4154 -4166.
AMA StyleClément Verkest, Emilie Piquet, Sylvie Diochot, Mélodie Dauvois, Michel Lanteri-Minet, Eric Lingueglia, Anne Baron. Effects of systemic inhibitors of acid-sensing ion channels 1 (ASIC1) against acute and chronic mechanical allodynia in a rodent model of migraine. British Journal of Pharmacology. 2018; 175 (21):4154-4166.
Chicago/Turabian StyleClément Verkest; Emilie Piquet; Sylvie Diochot; Mélodie Dauvois; Michel Lanteri-Minet; Eric Lingueglia; Anne Baron. 2018. "Effects of systemic inhibitors of acid-sensing ion channels 1 (ASIC1) against acute and chronic mechanical allodynia in a rodent model of migraine." British Journal of Pharmacology 175, no. 21: 4154-4166.
Anne Baron; Sylvie Diochot; Miguel Salinas; Abdelkrim Alloui; Dominique Douguet; Gilles Mourier; Pascal Kessler; Enrico A. Stura; Thomas Besson; Valérie Friend; Denis Servent; Alain Eschalier; Eric Lingueglia. Mambalgins, snake peptides against inflammatory and neuropathic pain through inhibition of ASIC channels. Toxicon 2018, 149, 93 .
AMA StyleAnne Baron, Sylvie Diochot, Miguel Salinas, Abdelkrim Alloui, Dominique Douguet, Gilles Mourier, Pascal Kessler, Enrico A. Stura, Thomas Besson, Valérie Friend, Denis Servent, Alain Eschalier, Eric Lingueglia. Mambalgins, snake peptides against inflammatory and neuropathic pain through inhibition of ASIC channels. Toxicon. 2018; 149 ():93.
Chicago/Turabian StyleAnne Baron; Sylvie Diochot; Miguel Salinas; Abdelkrim Alloui; Dominique Douguet; Gilles Mourier; Pascal Kessler; Enrico A. Stura; Thomas Besson; Valérie Friend; Denis Servent; Alain Eschalier; Eric Lingueglia. 2018. "Mambalgins, snake peptides against inflammatory and neuropathic pain through inhibition of ASIC channels." Toxicon 149, no. : 93.
Sylvie Diochot. Erratum to Chapter: Pain-Modulating Peptides in Spider Venoms: Good and Evil. Spider Venoms 2016, E1 -E1.
AMA StyleSylvie Diochot. Erratum to Chapter: Pain-Modulating Peptides in Spider Venoms: Good and Evil. Spider Venoms. 2016; ():E1-E1.
Chicago/Turabian StyleSylvie Diochot. 2016. "Erratum to Chapter: Pain-Modulating Peptides in Spider Venoms: Good and Evil." Spider Venoms , no. : E1-E1.
While few spiders are responsible for human envenomations of medical importance, their venom contains a large variety of bio-active molecules, able to modulate neuronal ion channels and receptors. These Neurotoxins involved in the paralysis of prey and toxicity during human envenomation have been extensively studied. Some of them helped to demonstrate the role of ion channels subtypes and receptors in pain processing. In spider venoms, molecules such as biogenic amines, ATP or NGF have a role in the induction of pain. Polyamines, by blocking NMDA channels, induce prey paralysis, but some are also able to modulate TRPV1 and AMPA channels involved in pain transmission. Many peptide toxins, which share a common structure, a compact cysteine knot, activate voltage-gated sodium channels and have a synergistic action to induce pain. More recently isolated peptides have shown analgesic effects by modulating ion channels such as voltage-gated calcium channels, ASICs, P2X3, and SACs. Some of these neurotoxins could be the basis for the development of future analgesics.
Sylvie Diochot. Pain Modulating Peptides in Spider Venoms: Good and Evil. Spider Venoms 2016, 1 -26.
AMA StyleSylvie Diochot. Pain Modulating Peptides in Spider Venoms: Good and Evil. Spider Venoms. 2016; ():1-26.
Chicago/Turabian StyleSylvie Diochot. 2016. "Pain Modulating Peptides in Spider Venoms: Good and Evil." Spider Venoms , no. : 1-26.
Mambalgins are 57-amino acid peptides isolated from snake venom that evoke naloxone-resistant analgesia after local (intraplantar) and central (intrathecal) injections through inhibition of particular subtypes of acid-sensing ion channels (ASICs). We now show that mambalgins also have an opioid-independent effect on both thermal and mechanical inflammatory pain after systemic intravenous (i.v.) administration and are effective against neuropathic pain. By combining the use of knockdown and knockout animals, we show the critical involvement of peripheral ASIC1b-containing channels, along with a contribution of ASIC1a-containing channels, in the i.v. effects of these peptides against inflammatory pain. The potent analgesic effect on neuropathic pain involves 2 different mechanisms depending on the route of administration, a naloxone-insensitive and ASIC1a-independent effect associated with i.v. injection and an ASIC1a-dependent and partially naloxone-sensitive effect associated with intrathecal injection. These data further support the role of peripheral and central ASIC1-containing channels in pain, demonstrate their participation in neuropathic pain, and highlight differences in the repertoire of channels involved in different pain conditions. They also strengthen the therapeutic potential of mambalgin peptides that are active in a broader range of experimental pain models and through i.v. systemic delivery.
Sylvie Diochot; Abdelkrim Alloui; Précillia Rodrigues; Mélodie Dauvois; Valérie Friend; Youssef Aissouni; Alain Eschalier; Eric Lingueglia; Anne Baron. Analgesic effects of mambalgin peptide inhibitors of acid-sensing ion channels in inflammatory and neuropathic pain. Pain 2016, 157, 552 -559.
AMA StyleSylvie Diochot, Abdelkrim Alloui, Précillia Rodrigues, Mélodie Dauvois, Valérie Friend, Youssef Aissouni, Alain Eschalier, Eric Lingueglia, Anne Baron. Analgesic effects of mambalgin peptide inhibitors of acid-sensing ion channels in inflammatory and neuropathic pain. Pain. 2016; 157 (3):552-559.
Chicago/Turabian StyleSylvie Diochot; Abdelkrim Alloui; Précillia Rodrigues; Mélodie Dauvois; Valérie Friend; Youssef Aissouni; Alain Eschalier; Eric Lingueglia; Anne Baron. 2016. "Analgesic effects of mambalgin peptide inhibitors of acid-sensing ion channels in inflammatory and neuropathic pain." Pain 157, no. 3: 552-559.
While few spiders are responsible for human envenomations of medical importance, their venom contains a large variety of bio-active molecules, able to modulate neuronal ion channels and receptors. These Neurotoxins involved in the paralysis of prey and toxicity during human envenomation have been extensively studied. Some of them helped to demonstrate the role of ion channels subtypes and receptors in pain processing. In spider venoms, molecules such as biogenic amines, ATP or NGF have a role in the induction of pain. Polyamines, by blocking NMDA channels, induce prey paralysis, but some are also able to modulate TRPV1 and AMPA channels involved in pain transmission. Many peptide toxins, which share a common structure, a compact cysteine knot, activate voltage-gated sodium channels and have a synergistic action to induce pain. More recently isolated peptides have shown analgesic effects by modulating ion channels such as voltage-gated calcium channels, ASICs, P2X3, and SACs. Some of these neurotoxins could be the basis for the development of future analgesics.
Diochot Sylvie. Pain Modulating Peptides in Spider Venoms: Good and Evil. Spider Venoms 2015, 1 -26.
AMA StyleDiochot Sylvie. Pain Modulating Peptides in Spider Venoms: Good and Evil. Spider Venoms. 2015; ():1-26.
Chicago/Turabian StyleDiochot Sylvie. 2015. "Pain Modulating Peptides in Spider Venoms: Good and Evil." Spider Venoms , no. : 1-26.