FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200504151> ?p ?o ?g. }

• W4200504151 endingPage "13541" @default.
• W4200504151 startingPage "13541" @default.
• W4200504151 abstract "Voltage-gated Na+ (Nav) channels are the primary molecular determinant of the action potential. Among the nine isoforms of the Nav channel α subunit that have been described (Nav1.1-Nav1.9), Nav1.1, Nav1.2, and Nav1.6 are the primary isoforms expressed in the central nervous system (CNS). Crucially, these three CNS Nav channel isoforms display differential expression across neuronal cell types and diverge with respect to their subcellular distributions. Considering these differences in terms of their localization, the CNS Nav channel isoforms could represent promising targets for the development of targeted neuromodulators. However, current therapeutics that target Nav channels lack selectivity, which results in deleterious side effects due to modulation of off-target Nav channel isoforms. Among the structural components of the Nav channel α subunit that could be pharmacologically targeted to achieve isoform selectivity, the C-terminal domains (CTD) of Nav channels represent promising candidates on account of displaying appreciable amino acid sequence divergence that enables functionally unique protein-protein interactions (PPIs) with Nav channel auxiliary proteins. In medium spiny neurons (MSNs) of the nucleus accumbens (NAc), a critical brain region of the mesocorticolimbic circuit, the PPI between the CTD of the Nav1.6 channel and its auxiliary protein fibroblast growth factor 14 (FGF14) is central to the generation of electrical outputs, underscoring its potential value as a site for targeted neuromodulation. Focusing on this PPI, we previously developed a peptidomimetic derived from residues of FGF14 that have an interaction site on the CTD of the Nav1.6 channel. In this work, we show that whereas the compound displays dose-dependent effects on the activity of Nav1.6 channels in heterologous cells, the compound does not affect Nav1.1 or Nav1.2 channels at comparable concentrations. In addition, we show that the compound correspondingly modulates the action potential discharge and the transient Na+ of MSNs of the NAc. Overall, these results demonstrate that pharmacologically targeting the FGF14 interaction site on the CTD of the Nav1.6 channel is a strategy to achieve isoform-selective modulation, and, more broadly, that sites on the CTDs of Nav channels interacted with by auxiliary proteins could represent candidates for the development of targeted therapeutics." @default.
• W4200504151 created "2021-12-31" @default.
• W4200504151 creator A5009703605 @default.
• W4200504151 creator A5018666743 @default.
• W4200504151 creator A5023901418 @default.
• W4200504151 creator A5054146317 @default.
• W4200504151 creator A5057960576 @default.
• W4200504151 creator A5061801349 @default.
• W4200504151 creator A5074240037 @default.
• W4200504151 creator A5081470417 @default.
• W4200504151 creator A5091415447 @default.
• W4200504151 date "2021-12-17" @default.
• W4200504151 modified "2023-10-16" @default.
• W4200504151 title "Pharmacologically Targeting the Fibroblast Growth Factor 14 Interaction Site on the Voltage-Gated Na+ Channel 1.6 Enables Isoform-Selective Modulation" @default.
• W4200504151 cites W1576533924 @default.
• W4200504151 cites W1877667838 @default.
• W4200504151 cites W1969443253 @default.
• W4200504151 cites W1971198708 @default.
• W4200504151 cites W1980176764 @default.
• W4200504151 cites W1981878280 @default.
• W4200504151 cites W1990800058 @default.
• W4200504151 cites W2000681405 @default.
• W4200504151 cites W2001473063 @default.
• W4200504151 cites W2004583716 @default.
• W4200504151 cites W2008093629 @default.
• W4200504151 cites W2023180078 @default.
• W4200504151 cites W2026945534 @default.
• W4200504151 cites W2038397615 @default.
• W4200504151 cites W2039072874 @default.
• W4200504151 cites W2041526142 @default.
• W4200504151 cites W2044170499 @default.
• W4200504151 cites W2048111738 @default.
• W4200504151 cites W2056169996 @default.
• W4200504151 cites W2061321767 @default.
• W4200504151 cites W2067712920 @default.
• W4200504151 cites W2085957678 @default.
• W4200504151 cites W2093258733 @default.
• W4200504151 cites W2095345152 @default.
• W4200504151 cites W2108712999 @default.
• W4200504151 cites W2110705761 @default.
• W4200504151 cites W2131966406 @default.
• W4200504151 cites W2147865003 @default.
• W4200504151 cites W2152823272 @default.
• W4200504151 cites W2155296569 @default.
• W4200504151 cites W2158164249 @default.
• W4200504151 cites W2166637802 @default.
• W4200504151 cites W2167398093 @default.
• W4200504151 cites W2297211792 @default.
• W4200504151 cites W2322283348 @default.
• W4200504151 cites W2362384227 @default.
• W4200504151 cites W2487829348 @default.
• W4200504151 cites W2562357591 @default.
• W4200504151 cites W2582255964 @default.
• W4200504151 cites W2608788973 @default.
• W4200504151 cites W2623777044 @default.
• W4200504151 cites W2784550580 @default.
• W4200504151 cites W2797545321 @default.
• W4200504151 cites W2835989029 @default.
• W4200504151 cites W2891239553 @default.
• W4200504151 cites W2897541226 @default.
• W4200504151 cites W2905114931 @default.
• W4200504151 cites W2928930495 @default.
• W4200504151 cites W2944198755 @default.
• W4200504151 cites W2946185511 @default.
• W4200504151 cites W2976553517 @default.
• W4200504151 cites W2996435836 @default.
• W4200504151 cites W3007130283 @default.
• W4200504151 cites W3021679920 @default.
• W4200504151 cites W3037224757 @default.
• W4200504151 cites W3043336915 @default.
• W4200504151 cites W3045251346 @default.
• W4200504151 cites W3093155940 @default.
• W4200504151 cites W3164128464 @default.
• W4200504151 cites W3188831673 @default.
• W4200504151 cites W3196682570 @default.
• W4200504151 cites W3214010716 @default.
• W4200504151 cites W4250465214 @default.
• W4200504151 cites W4376453232 @default.
• W4200504151 doi "https://doi.org/10.3390/ijms222413541" @default.
• W4200504151 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34948337" @default.
• W4200504151 hasPublicationYear "2021" @default.
• W4200504151 type Work @default.
• W4200504151 citedByCount "2" @default.
• W4200504151 countsByYear W42005041512022 @default.
• W4200504151 countsByYear W42005041512023 @default.
• W4200504151 crossrefType "journal-article" @default.
• W4200504151 hasAuthorship W4200504151A5009703605 @default.
• W4200504151 hasAuthorship W4200504151A5018666743 @default.
• W4200504151 hasAuthorship W4200504151A5023901418 @default.
• W4200504151 hasAuthorship W4200504151A5054146317 @default.
• W4200504151 hasAuthorship W4200504151A5057960576 @default.
• W4200504151 hasAuthorship W4200504151A5061801349 @default.
• W4200504151 hasAuthorship W4200504151A5074240037 @default.
• W4200504151 hasAuthorship W4200504151A5081470417 @default.
• W4200504151 hasAuthorship W4200504151A5091415447 @default.
• W4200504151 hasBestOaLocation W42005041511 @default.
• W4200504151 hasConcept C104292427 @default.
• W4200504151 hasConcept C104317684 @default.

• next