IndraLab

Statements

FGF13 binds SCN9A. 20 / 21
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sparser
"Compound PW164 was identified as a selective FGF13-Nav1.7 attenuator with analgesic activity."
40662358
sparser
"Singh, Bernabucci, and colleagues used multiple techniques to determine how the FGF13 interaction with Nav1.7 modulates current properties, neuronal excitability, and pain sensations ( xref )."
40662358
sparser
"Using protein-protein interaction assays, they identified a molecule with drug-like properties, PW164, that bound at the FGF13-Nav1.7 interface."
40662358
sparser
"PW164 inhibited FGF13 binding to Nav1.7 and blocked the ability of FGF13 to upregulate Nav1.7 current density ( xref )."
40662358
sparser
"This finding suggests a role for the FGF13-Nav1.7 complex in hypersensitivity following exposure to noxious stimuli."
40662358
sparser
"To explore the role of the FGF13-Nav1.7 interaction in a more clinically relevant pain model, the authors tested PW164 in a mouse model of type-2 diabetic neuropathy (T2DN)."
40662358
sparser
"Additional screens also identified the small molecule ZL192 that (a) stabilized the FGF13-Nav1.7 interaction, (b) potentiated Nav1.7 currents when FGF13 was also present, and (c) induced robust mechanical hyperalgesia and thermal hypersensitivity in mice."
40662358
sparser
"This result further validated the importance of the FGF13-Nav1.7 interaction in regulating pain sensitivity."
40662358
sparser
"While the lack of effect on blood pressure in mice is encouraging, future studies will be critical to determine if manipulating the FGF13-Nav1.7 interaction in humans has impact on any aspects of sympathetic function in humans."
40662358
sparser
"While Singh, Bernabucci, and authors provide an array of evidence that FGF13 is a critical player in modulating pain sensitivity ( xref ), it is important to determine how selectively the FGF13-Nav1.7 interaction in nociceptive neurons can be targeted."
40662358
sparser
"Is PW164 specific enough in its actions and/or is it possible to generate more specific inhibitors of the FGF13-Nav1.7 interface?"
40662358
sparser
"Understanding the nuances in specificity may be crucial to pharmacological adjustment of the FGF13-Nav1.7 rheostat."
40662358
sparser
"It will be important to establish the full range of pain conditions that respond to disruption of the FGF13-Nav1.7 rheostat."
40662358
sparser
"Our data suggest that increased neuronal excitability after nerve injury might be triggered, in part, via a loss of FHF2-Nav1.7 interaction."
36222860
sparser
"In this study we investigated whether this interaction between FHF2 and Nav1.7 translates to increased excitability in DRG neurons."
36222860
reach
"Our immunohistochemical data show colocalization of FHF2A with Nav1.7 in small diameter DRG neurons, most of which are nociceptors, and immunoprecipiation experiments revealed an interaction between FHF2 and Nav1.7 in HEK293 cells, supporting the conclusion that the two proteins may interact in vivo."
31223136
sparser
"We have previously demonstrated that FHF2 interacts with Nav1.7 and that knockdown of FHF2A or FHF2core (all isoforms of FHF2) in DRG neurons results in gain-of-function changes in the gating properties of Nav1.7."
36222860
sparser
"These results suggest that increased DRG neuron excitability after nerve injury might occur in part via a Nav1.7-FHF2 mediated mechanism."
36222860
sparser
"Nav1.7 interactions with FGF13, also abundant in sensory neurons ( xref ), mediate noxious stimuli–induced cellular signaling ( xref ), a process typically activated by the transient receptor potential cation channel subfamily V member 1 (TRPV1) ( xref , xref )."
40662354
signor
"Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels."
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