Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels

International audienceAcid-sensing ion channels (ASICs) are voltage-independent proton-gated cation channels that are largely expressed in the nervous system as well as in some non-neuronal tissues. In rodents, six different isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) can associate into homo-or hetero-trimers to form a functional channel. Specific polypeptide toxins targeting ASIC channels have been isolated from the venoms of spider (PcTx1), sea anemone (APETx2) and snakes (MitTx and mambalgins). They exhibit different and sometimes partially overlapping pharmacological profiles and are usually blockers of ASIC channels, except for MitTx, which is a potent activator. This review focuses on the use of these toxins to explore the structure-function relationships, the physiological and the pathophysiological roles of ASIC channels, illustrating at the same time the therapeutic potential of some of these natural compounds

Toxins: what’s up, doc?

Natural substances have been of interest for several centuries and many toxins of animal, plant, bacterial or fungal origins have been identified and characterized. The evolution of technologies applied to biotoxinology has permitted considerable progress in the deciphering of their structure, of the molecular bases of their interaction with their specific receptors, and of their role in neutralizing living organisms. Artificial intelligence tolerates the accumulation of a considerable amount of exploitable data, a progress leading to wide genomic and proteomic analyses and the establishment of robust models, which in turn can be used to identify new molecules of therapeutic interest through their functional identification and evolution. Toxin detection methods for early and highly specific diagnosis in public health, along with the understanding of their interactions at the cellular or tissue level, have also been improved owing to the use of biosensors. In this Special Issue of the journal Toxins, entitled “Toxins: What's up, Doc?”, research and review articles concerning the latest discoveries in the field of venoms and toxinology will be presented to cover broad areas ranging from the composition and evolution of venoms to the mechanism of action, structural conservation versus variability, and therapeutic applicability of toxins. This special issue is open, albeit not restricted, to those communications that were presented during the 28th Meeting of Toxinology (RT28) organized by the French Society of Toxinology (SFET) on the 28th and 29th of November 2022 at the Institut Pasteur of Paris

Toxins: what’s up, doc?

Natural substances have been of interest for several centuries and many toxins of animal, plant, bacterial or fungal origins have been identified and characterized. The evolution of technologies applied to biotoxinology has permitted considerable progress in the deciphering of their structure, of the molecular bases of their interaction with their specific receptors, and of their role in neutralizing living organisms. Artificial intelligence tolerates the accumulation of a considerable amount of exploitable data, a progress leading to wide genomic and proteomic analyses and the establishment of robust models, which in turn can be used to identify new molecules of therapeutic interest through their functional identification and evolution. Toxin detection methods for early and highly specific diagnosis in public health, along with the understanding of their interactions at the cellular or tissue level, have also been improved owing to the use of biosensors. In this Special Issue of the journal Toxins, entitled “Toxins: What's up, Doc?”, research and review articles concerning the latest discoveries in the field of venoms and toxinology will be presented to cover broad areas ranging from the composition and evolution of venoms to the mechanism of action, structural conservation versus variability, and therapeutic applicability of toxins. This special issue is open, albeit not restricted, to those communications that were presented during the 28th Meeting of Toxinology (RT28) organized by the French Society of Toxinology (SFET) on the 28th and 29th of November 2022 at the Institut Pasteur of Paris

Report from the 28th Meeting on Toxinology, “Toxins: What’s up, Doc?”, Organized by the French Society of Toxinology on 28–29 November 2022

International audienceThe French Society of Toxinology (SFET) organized its 28th annual meeting on 28–29 November 2022 (RT28). The central theme of this meeting was “Toxins: What’s up, Doc?”, emphasizing the latest findings on animal, bacterial, algal, plant and fungal toxins through sessions dedicated to deep learning, toxin tracking and toxinomic advances, shared by ca. 80 participants. The abstracts of the 10 invited and 11 selected lectures and 15 posters, along with the names of the Best Oral Communication and Best Poster awardees, are presented in this report

Report from the 28th Meeting on Toxinology, “Toxins: What’s up, Doc?”, Organized by the French Society of Toxinology on 28–29 November 2022

International audienceThe French Society of Toxinology (SFET) organized its 28th annual meeting on 28–29 November 2022 (RT28). The central theme of this meeting was “Toxins: What’s up, Doc?”, emphasizing the latest findings on animal, bacterial, algal, plant and fungal toxins through sessions dedicated to deep learning, toxin tracking and toxinomic advances, shared by ca. 80 participants. The abstracts of the 10 invited and 11 selected lectures and 15 posters, along with the names of the Best Oral Communication and Best Poster awardees, are presented in this report

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

International audienc

Report from the 28th Meeting on Toxinology, “Toxins: What’s up, Doc?”, Organized by the French Society of Toxinology on 28–29 November 2022

The French Society of Toxinology (SFET) organized its 28th annual meeting on 28–29 November 2022 (RT28). The central theme of this meeting was “Toxins: What’s up, Doc?”, emphasizing the latest findings on animal, bacterial, algal, plant and fungal toxins through sessions dedicated to deep learning, toxin tracking and toxinomic advances, shared by ca. 80 participants. The abstracts of the 10 invited and 11 selected lectures and 15 posters, along with the names of the Best Oral Communication and Best Poster awardees, are presented in this report

Report from the 29th Meeting on Toxinology, “Toxins: From the Wild to the Lab”, Organized by the French Society of Toxinology on 30 November–1 December 2023

International audienceThe French Society of Toxinology (SFET), which celebrated its 30th anniversary this year, organized its 29th annual Meeting (RT29), shared by 87 participants, on 30 November–1 December 2023. The RT29 main theme, “Toxins: From the Wild to the Lab”, focused on research in the field of animal venoms and animal, bacterial, fungal, or plant toxins, from their discovery in nature to their study in the laboratory. The exploration of the functions of toxins, their structures, their molecular or cellular ligands, their mode of action, and their potential therapeutic applications were emphasized during oral communications and posters through three sessions, of which each was dedicated to a secondary theme. A fourth, “miscellaneous” session allowed participants to present recent out-of-theme works. The abstracts of nine invited and 15 selected lectures, those of 24 posters, and the names of the Best Oral Communication and Best Poster awardees, are presented in this report

Mechanisms of Action of the Peptide Toxins Targeting Human and Rodent Acid-Sensing Ion Channels and Relevance to Their In Vivo Analgesic Effects

Acid-sensing ion channels (ASICs) are voltage-independent H+-gated cation channels largely expressed in the nervous system of rodents and humans. At least six isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) associate into homotrimers or heterotrimers to form functional channels with highly pH-dependent gating properties. This review provides an update on the pharmacological profiles of animal peptide toxins targeting ASICs, including PcTx1 from tarantula and related spider toxins, APETx2 and APETx-like peptides from sea anemone, and mambalgin from snake, as well as the dimeric protein snake toxin MitTx that have all been instrumental to understanding the structure and the pH-dependent gating of rodent and human cloned ASICs and to study the physiological and pathological roles of native ASICs in vitro and in vivo. ASICs are expressed all along the pain pathways and the pharmacological data clearly support a role for these channels in pain. ASIC-targeting peptide toxins interfere with ASIC gating by complex and pH-dependent mechanisms sometimes leading to opposite effects. However, these dual pH-dependent effects of ASIC-inhibiting toxins (PcTx1, mambalgin and APETx2) are fully compatible with, and even support, their analgesic effects in vivo, both in the central and the peripheral nervous system, as well as potential effects in humans

Current perspectives on acid-sensing ion channels: new advances and therapeutic implications

International audienc