Venom-derived modulators of epilepsy-related ion channels
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Absalom, Nathan
Biggs, Kimberley
King, Glenn F
Ma, Linlin
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Abstract
Epilepsy is characterised by spontaneous recurrent seizures that are caused by an imbalance between neuronal excitability and inhibition. Since ion channels play fundamental roles in the generation and propagation of action potentials as well as neurotransmitter release at a subset of excitatory and inhibitory synapses, their dysfunction has been linked to a wide variety of epilepsies. Indeed, these unique proteins are the major biological targets for antiepileptic drugs. Selective targeting of a specific ion channel subtype remains challenging for small molecules, due to the high level of homology among members of the same channel family. As a consequence, there is a growing trend to target ion channels with biologics. Venoms are the best known natural source of ion channel modulators, and venom peptides are increasingly recognised as potential therapeutics due to their high selectivity and potency gained through millions of years of evolutionary selection pressure. Here we describe the major ion channel families involved in the pathogenesis of various types of epilepsy, including voltage-gated Na+, K+, Ca2+ channels, Cys-loop receptors, ionototropic glutamate receptors and P2X receptors, and currently available venom-derived peptides that target these channel proteins. Although only a small number of venom peptides have successfully progressed to the clinic, there is reason to be optimistic about their development as anti-epileptic drugs, notwithstanding the challenges associated with development of any class of peptide drug.
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Biochemical Pharmacology
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© 2020 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
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Biochemistry and cell biology
Pharmacology and pharmaceutical sciences
epilepsy
ion channel
venom peptide
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Citation
Yuen Chow, C; Absalom, N; Biggs, K; King, GF; Ma, L, Venom-derived modulators of epilepsy-related ion channels, Biochemical Pharmacology, 2020