Enhanced motivated behavior mediated by pharmacological targeting of the FGF14/Na_v1.6 complex in nucleus accumbens neurons.

ABSTRACT: Protein/protein interactions (PPI) play crucial roles in neuronal functions. Yet, their potential as drug targets for brain disorders remains underexplored. The fibroblast growth factor 14 (FGF14)/voltage-gated Na⁺ channel 1.6 (Na_v1.6) complex regulates excitability of medium spiny neurons (MSN) of the nucleus accumbens (NAc), a central hub of reward circuitry that controls motivated behaviors. Here, we identified compound 1028 (IUPAC: ethyl 3-(2-(3-(hydroxymethyl)-1H-indol-1-yl)acetamido)benzoate), a brain-permeable small molecule that targets FGF14^R117, a critical residue located within a druggable pocket at the FGF14/Na_v1.6 PPI interface. We found that 1028 modulates FGF14/Na_v1.6 complex assembly and depolarizes the voltage-dependen

SUBMITTER: Dvorak NM 

PROVIDER: S-EPMC11696184 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature