Identification and targeting of a unique Na_V1.7 domain driving chronic pain.

ABSTRACT: Small molecules directly targeting the voltage-gated sodium channel (VGSC) Na_V1.7 have not been clinically successful. We reported that preventing the addition of a small ubiquitin-like modifier onto the Na_V1.7-interacting cytosolic collapsin response mediator protein 2 (CRMP2) blocked Na_V1.7 function and was antinociceptive in rodent models of neuropathic pain. Here, we discovered a CRMP2 regulatory sequence (CRS) unique to Na_V1.7 that is essential for this regulatory coupling. CRMP2 preferentially bound to the Na_V1.7 CRS over other Na_V isoforms. Substitution of the Na_V1.7 CRS with the homologous domains from the other eight VGSC isoforms decreased Na_V1.7 currents. A cell-penetrant decoy peptide corres

SUBMITTER: Gomez K 

PROVIDER: S-EPMC10410761 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature