Therapeutic potential of venom peptides

Lewis, Richard J.; García, María L.

doi:10.1038/nrd1197

Cited by 678 publications

(495 citation statements)

References 129 publications

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“…Venoms from cone snails provide interesting libraries of peptide toxins displaying a high affinity for voltage-or ligand-gated ion channels and have been successfully used as structural probes to characterize nAChRs [9,46,47]. α-conotoxins, that specifically target nAChRs, display a consensus fold with a central helical region braced by two conserved disulphide bridges ( Figure 7).…”

Section: Investigating Switches In Nachr Selectivity Between Differenmentioning

confidence: 99%

Insight in nAChR subtype selectivity from AChBP crystal structures

Rucktooa

Smit²,

Sixma

2009

Biochemical Pharmacology

116

117

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Nicotinic acetylcholine receptors (nAChRs) display a broad variety of subtypes, which in turn present a complex subcellular and regional expression pattern in the brain, as well as a specific pharmacological profile. The association of these nAChRs with different types of brain disease has turned them into interesting drug targets for the treatment of Alzheimer's disease or schizophrenia, or for anti-smoking compounds among others. In the same way, muscle-type nAChRs present at neuromuscular junctions are also being targeted by muscle relaxants. However, to date no high-resolution structural data is available on functional

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Section: Investigating Switches In Nachr Selectivity Between Differenmentioning

confidence: 99%

Insight in nAChR subtype selectivity from AChBP crystal structures

Rucktooa

Smit²,

Sixma

2009

Biochemical Pharmacology

116

117

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“…The enormous diversity of peptides from Conus snails that target ion channels, receptors, and transporters known to be involved in neuropathic pain has led to the search for better analgesics based on venom-derived peptides (Lewis and Garcia 2003). The α-conotoxins represent one such family that specifically target nicotinic acetylcholine receptor (nAChR) subtypes.…”

Section: Introductionmentioning

confidence: 99%

Intrathecal α-conotoxins Vc1.1, AuIB and MII acting on distinct nicotinic receptor subtypes reverse signs of neuropathic pain

et al. 2012

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The large diversity of peptides from venomous creatures with high affinity for molecules involved in the development and maintenance of neuropathic pain has led to a surge in venom-derived analgesic research. Some members of the α-conotoxin family from Conus snails which specifically target subtypes of nicotinic acetylcholine receptors (nAChR) have been shown to be effective at reducing mechanical allodynia in neuropathic pain models. We sought to determine if three such peptides, Vc1.1, AuIB and MII were effective following intrathecal administration in a rat neuropathic pain model because they exhibit different affinities for the major putative pain relieving targets of α-conotoxins. Intrathecal administration of α-conotoxins, Vc1.1, AuIB and MII into neuropathic rats reduced mechanical allodynia for up to 6 hours without significant side effects. In vitro patch-clamp electrophysiology of primary afferent synaptic transmission revealed the mode of action of these toxins was not via a GABA B -dependant mechanism, and is more likely related to their action at nAChRs containing combinations of α3, α7 or other subunits. Intrathecal nAChR subunitselective conotoxins are therefore promising tools for the effective treatment of neuropathic pain. AbstractThe large diversity of peptides from venomous creatures with high affinity for molecules involved in the development and maintenance of neuropathic pain has led to a surge in venom-derived analgesic research. Some members of the α-conotoxin family from Conus snails which specifically target subtypes of nicotinic acetylcholine receptors (nAChR) have been shown to be effective at reducing mechanical allodynia in neuropathic pain models. We sought to determine if three such peptides, Vc1.1, AuIB and MII were effective following intrathecal administration in a rat neuropathic pain model because they exhibit different affinities for the major putative pain relieving targets of α-conotoxins. Intrathecal administration of α-conotoxins, Vc1.1, AuIB and MII into neuropathic rats reduced mechanical allodynia for up to 6 hours without significant side effects. In vitro patch-clamp electrophysiology of primary afferent synaptic transmission revealed the mode of action of these toxins was not via a GABA B -dependant mechanism, and is more likely related to their action at nAChRs containing combinations of α3, α7 or other subunits. Intrathecal nAChR subunitselective conotoxins are therefore promising tools for the effective treatment of neuropathic pain.3

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“…Sua estabilidade estrutural, facilidade de síntese, elevada especifi cidade de alvo e pequeno tamanho de seus peptídeos, proporcionam-lhes um importante potencial terapêutico (SHEN et al, 2000;LEWIS & GARCIA, 2003;OLIVERA & TEICHERT, 2007). Assim, esta revisão objetiva discorrer sobre a fi siopatologia do TME, com ênfase na importância do cálcio (Ca 2+ ) no mecanismo de morte neuronal, abordando a possível utilização terapêutica das toxinas de caramujo marinho bloqueadoras de canais para Ca 2+ dependentes de voltagem (CCDV).…”

Section: Introductionunclassified