Selective Targeting of Nav1.7 with Engineered Spider Venom-Based Peptides.

Abstract:

:A fundamental mechanism that drives the propagation of electrical signals in the nervous system is the activation of voltage-gated sodium channels. The sodium channel subtype Nav1.7 is critical for the transmission of pain-related signaling, with gain-of-function mutations in Nav1.7 resulting in various painful pathologies. Loss-of-function mutations cause complete insensitivity to pain and anosmia in humans that otherwise have normal nervous system function, rendering Nav1.7 an attractive target for the treatment of pain. Despite this, no Nav1.7 selective therapeutic has been approved for use as an analgesic to date. Here we present a summary of research that has focused on engineering peptides found in spider venoms to produce Nav1.7 selective antagonists. We discuss the progress that has been made on various scaffolds from different venom families and highlight the challenges that remain in the effort to produce a Nav1.7 selective, venom-based analgesic.

journal_name

Channels (Austin)

journal_title

Channels (Austin, Tex.)

authors

Neff RA,Wickenden AD

doi

10.1080/19336950.2020.1860382

keywords:

["NAV1.7","Spider toxin","analgesic","antagonist","molecular modeling","neurotoxin","pain","peptide biosynthesis","review","sodium channel"]

subject

Has Abstract

pub_date

2021-12-01 00:00:00

pages

179-193

issue

1

eissn

1933-6950

issn

1933-6969

journal_volume

15

pub_type

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