Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways

Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways

Voltage-gated sodium channels (Na<sub>V</sub>s) are a key determinant of neuronal signalling. Neurotoxins from diverse taxa that selectively activate or inhibit Na<sub>V</sub> channels have helped unravel the role of Na<sub>V</sub> channels in diseases, including...

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Bibliographic Details
Main Authors: Yashad Dongol, Fernanda C. Cardoso, Richard J. Lewis
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Toxins
Subjects:
chronic pain
ick peptide
knottins
na<sub>v</sub>
spider venom
voltage-gated sodium channel
Online Access:https://www.mdpi.com/2072-6651/11/11/626
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spelling doaj-c4a5284461c34050abc6f549ddfa42382020-11-25T01:38:40ZengMDPI AGToxins2072-66512019-10-01111162610.3390/toxins11110626toxins11110626Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain PathwaysYashad Dongol0Fernanda C. Cardoso1Richard J. Lewis2Division of Chemistry and Structural Biology/Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, AustraliaDivision of Chemistry and Structural Biology/Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, AustraliaDivision of Chemistry and Structural Biology/Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, AustraliaVoltage-gated sodium channels (Na<sub>V</sub>s) are a key determinant of neuronal signalling. Neurotoxins from diverse taxa that selectively activate or inhibit Na<sub>V</sub> channels have helped unravel the role of Na<sub>V</sub> channels in diseases, including chronic pain. Spider venoms contain the most diverse array of inhibitor cystine knot (ICK) toxins (knottins). This review provides an overview on how spider knottins modulate Na<sub>V</sub> channels and describes the structural features and molecular determinants that influence their affinity and subtype selectivity. Genetic and functional evidence support a major involvement of Na<sub>V</sub> subtypes in various chronic pain conditions. The exquisite inhibitory properties of spider knottins over key Na<sub>V</sub> subtypes make them the best lead molecules for the development of novel analgesics to treat chronic pain.https://www.mdpi.com/2072-6651/11/11/626chronic painick peptideknottinsna<sub>v</sub>spider venomvoltage-gated sodium channel
collection DOAJ
language English
format Article
sources DOAJ
author Yashad Dongol
Fernanda C. Cardoso
Richard J. Lewis
spellingShingle Yashad Dongol
Fernanda C. Cardoso
Richard J. Lewis
Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways
Toxins
chronic pain
ick peptide
knottins
na<sub>v</sub>
spider venom
voltage-gated sodium channel
author_facet Yashad Dongol
Fernanda C. Cardoso
Richard J. Lewis
author_sort Yashad Dongol
title Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways
title_short Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways
title_full Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways
title_fullStr Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways
title_full_unstemmed Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways
title_sort spider knottin pharmacology at voltage-gated sodium channels and their potential to modulate pain pathways
publisher MDPI AG
series Toxins
issn 2072-6651
publishDate 2019-10-01
description Voltage-gated sodium channels (Na<sub>V</sub>s) are a key determinant of neuronal signalling. Neurotoxins from diverse taxa that selectively activate or inhibit Na<sub>V</sub> channels have helped unravel the role of Na<sub>V</sub> channels in diseases, including chronic pain. Spider venoms contain the most diverse array of inhibitor cystine knot (ICK) toxins (knottins). This review provides an overview on how spider knottins modulate Na<sub>V</sub> channels and describes the structural features and molecular determinants that influence their affinity and subtype selectivity. Genetic and functional evidence support a major involvement of Na<sub>V</sub> subtypes in various chronic pain conditions. The exquisite inhibitory properties of spider knottins over key Na<sub>V</sub> subtypes make them the best lead molecules for the development of novel analgesics to treat chronic pain.
topic chronic pain
ick peptide
knottins
na<sub>v</sub>
spider venom
voltage-gated sodium channel
url https://www.mdpi.com/2072-6651/11/11/626
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AT fernandaccardoso spiderknottinpharmacologyatvoltagegatedsodiumchannelsandtheirpotentialtomodulatepainpathways
AT richardjlewis spiderknottinpharmacologyatvoltagegatedsodiumchannelsandtheirpotentialtomodulatepainpathways
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