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Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways.
Toxins (Basel). 2019 10 29; 11(11)T

Abstract

Voltage-gated sodium channels (NaVs) are a key determinant of neuronal signalling. Neurotoxins from diverse taxa that selectively activate or inhibit NaV channels have helped unravel the role of NaV 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 NaV 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 NaV subtypes in various chronic pain conditions. The exquisite inhibitory properties of spider knottins over key NaV subtypes make them the best lead molecules for the development of novel analgesics to treat chronic pain.

Authors+Show Affiliations

Division of Chemistry and Structural Biology/Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Australia. y.dongol@imb.uq.edu.au.Division of Chemistry and Structural Biology/Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Australia. f.caldascardoso@imb.uq.edu.au.Division of Chemistry and Structural Biology/Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Australia. r.lewis@imb.uq.edu.au.

Pub Type(s)

Journal Article
Review
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31671792

Citation

Dongol, Yashad, et al. "Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways." Toxins, vol. 11, no. 11, 2019.
Dongol Y, Cardoso FC, Lewis RJ. Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways. Toxins (Basel). 2019;11(11).
Dongol, Y., Cardoso, F. C., & Lewis, R. J. (2019). Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways. Toxins, 11(11). https://doi.org/10.3390/toxins11110626
Dongol Y, Cardoso FC, Lewis RJ. Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways. Toxins (Basel). 2019 10 29;11(11) PubMed PMID: 31671792.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways. AU - Dongol,Yashad, AU - Cardoso,Fernanda Caldas, AU - Lewis,Richard J, Y1 - 2019/10/29/ PY - 2019/09/24/received PY - 2019/10/24/revised PY - 2019/10/24/accepted PY - 2019/11/2/entrez PY - 2019/11/2/pubmed PY - 2019/11/2/medline KW - ICK peptide KW - NaV KW - chronic pain KW - knottins KW - spider venom KW - voltage-gated sodium channel JF - Toxins JO - Toxins (Basel) VL - 11 IS - 11 N2 - Voltage-gated sodium channels (NaVs) are a key determinant of neuronal signalling. Neurotoxins from diverse taxa that selectively activate or inhibit NaV channels have helped unravel the role of NaV 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 NaV 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 NaV subtypes in various chronic pain conditions. The exquisite inhibitory properties of spider knottins over key NaV subtypes make them the best lead molecules for the development of novel analgesics to treat chronic pain. SN - 2072-6651 UR - https://www.unboundmedicine.com/medline/citation/31671792/Spider_Knottin_Pharmacology_at_Voltage_Gated_Sodium_Channels_and_Their_Potential_to_Modulate_Pain_Pathways_ L2 - https://www.mdpi.com/resolver?pii=toxins11110626 DB - PRIME DP - Unbound Medicine ER -
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