Affinage

NPAS4

Neuronal PAS domain-containing protein 4 · UniProt Q8IUM7

Length
802 aa
Mass
87.1 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NPAS4 is a neuron-specific, activity-induced bHLH-PAS transcription factor that translates patterns of neuronal activity into cell-type-specific gene programs governing excitatory/inhibitory balance, neuroprotection, and genome stability (PMID:18815592, PMID:24855953). It functions as a nuclear transcriptional activator that depends on obligate heterodimerization with the bHLH-PAS partners ARNT (ARNT1) and ARNT2 to bind DNA and transactivate target promoters and enhancers (e.g. the CNS midline enhancer motif), with ARNT2 being the predominant brain partner detected from native tissue (PMID:15363889, PMID:19284974); crystal structures of both NPAS4-ARNT and NPAS4-ARNT2 heterodimers on DNA reveal an interconnected domain conformation and variable PAS-A interfaces that distinguish the two complexes (PMID:36343253). Strikingly, distinct depolarizing stimuli channel NPAS4 into distinct dimers: action potentials drive NPAS4-ARNT and excitatory postsynaptic potentials drive NPAS4-ARNT2, and these stimulus-specific heterodimers occupy different genomic loci (PMID:31585079). Functionally, NPAS4 recruits RNA Polymerase II to activity-regulated genes and orchestrates opposing programs in different cell types — promoting inhibitory synapses onto excitatory neurons while promoting excitatory input onto inhibitory neurons (PMID:22194569, PMID:24855953). Its synaptic effects are executed through identified target genes, including BDNF for somatic inhibition, IQSEC3 in SST interneurons, and Plk2 and Homer1a/AMPA-receptor pathways that restrict excitatory synapse number and strength (PMID:24201284, PMID:34289353, PMID:29222951, PMID:29429933). NPAS4 also confers activity-dependent neuroprotection against excitotoxic and ischemic insult via downstream effectors Syt10 and Gem (which suppresses L-type VGCC Ca2+ influx) (PMID:26936998, PMID:34349016), and assembles a NuA4-TIP60 chromatin-modifying complex (NPAS4-NuA4) that recruits DNA repair machinery to recurrently damaged regulatory elements, coupling neuronal activity to genome maintenance and organismal lifespan (PMID:36792830). NPAS4 is a rapidly turned-over immediate-early gene whose expression is tightly gated by repressive inputs: glucocorticoid-receptor binding to negative GREs, HDAC3/HDAC5-dependent chromatin modification, REST/CTCF silencing in non-neuronal cells, promoter DNA methylation, and miRNA targeting of its 3'UTR (PMID:23020797, PMID:31883511, PMID:28957664, PMID:24291638, PMID:26222956).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2004 Medium

    Established NPAS4's molecular identity as a nuclear bHLH-PAS transcription factor that requires an ARNT partner to activate transcription, defining the dimerization-dependent mode of action.

    Evidence Overexpression, reporter gene assays and cellular fractionation in COS-7 cells

    PMID:15363889

    Open questions at the time
    • Did not identify endogenous neuronal target genes
    • Cell-line context, not neurons
    • Did not distinguish ARNT1 vs ARNT2 preference
  2. 2007 Medium

    Showed NPAS4 partners with ARNT2 and that its dosage is biologically critical — endogenous NPAS4 supports neuroprotection while sustained overexpression triggers apoptosis via Bax.

    Evidence Reporter assays, adenoviral overexpression and RNAi in F-11 cells with neuroprotection readout

    PMID:17214977

    Open questions at the time
    • Mechanism connecting NPAS4 to Bax activation not resolved
    • Single cell-line model
  3. 2008 High

    Identified NPAS4's first defining physiological role: controlling activity-dependent development of inhibitory synapses onto excitatory neurons and thereby E/I homeostasis.

    Evidence Loss-of-function in neurons with inhibitory synapse number readout and activity-dependent gene expression analysis

    PMID:18815592

    Open questions at the time
    • Direct target genes mediating synapse number not yet defined
    • Did not address other neuronal cell types
  4. 2009 High

    Confirmed in native brain that NPAS4 forms functional heterodimers with both ARNT1 and ARNT2, with ARNT2 predominant, grounding the dimer model in vivo.

    Evidence Co-IP from whole brain extracts, in vitro co-precipitation, and yeast two-hybrid

    PMID:19284974

    Open questions at the time
    • Did not establish what selects ARNT1 vs ARNT2
    • No genome-wide binding data
  5. 2013 Medium

    Demonstrated genetically that NPAS4 is required for neuroprotective preconditioning and that its loss causes age-dependent neurodegeneration and excitotoxic vulnerability.

    Evidence NXF knockout mice, glutamate excitotoxicity model, histology and reporter assays

    PMID:19001414

    Open questions at the time
    • Downstream neuroprotective effectors not yet identified
    • Mechanism of neurodegeneration not resolved
  6. 2011 High

    Linked NPAS4 to behavior and a transcriptional mechanism: it recruits RNA Pol II to activity-regulated promoters/enhancers in CA3 and is required for contextual memory, with restoration rescuing the deficit.

    Evidence Region-selective KO plus viral rescue, ChIP for RNA Pol II, contextual fear memory assay

    PMID:22194569

    Open questions at the time
    • Specific memory-relevant target genes not enumerated
    • Mechanism of Pol II recruitment not detailed
  7. 2013 High

    Resolved the spatial logic of NPAS4-controlled inhibition in vivo, showing it redistributes inhibitory synapses (soma up, dendrite down) with BDNF as the direct effector of somatic inhibition.

    Evidence In vivo loss-of-function with compartment-resolved synapse quantification and Bdnf epistasis

    PMID:24201284

    Open questions at the time
    • Effector for dendritic inhibition not identified
    • How a single TF produces opposite compartmental effects unresolved
  8. 2014 High

    Generalized NPAS4 as a cell-type-specific orchestrator: it activates distinct late-response programs in excitatory vs inhibitory neurons producing opposite synaptic outcomes in each.

    Evidence Conditional KO, RNA-seq, and electrophysiology in two neuronal cell types

    PMID:24855953

    Open questions at the time
    • Determinants of cell-type-specific genomic targeting unknown
  9. 2014 Medium

    Established the functional requirement for ARNT2 dimerization through human disease-associated variants, mapping F147 to the dimer interface and tying dimerization to BDNF activation.

    Evidence Luciferase reporter, Co-IP, endogenous BDNF assay, NLS microscopy and homology modelling with human variants

    PMID:24465693

    Open questions at the time
    • Clinical penetrance of variants not established here
    • Structural model only by homology
  10. 2016 Medium

    Identified Syt10 as a direct neuroprotective effector downstream of NPAS4, providing a molecular route from activity to excitotoxicity resistance.

    Evidence Syt10 KO neurons, NPAS4 gain/loss-of-function, kainate excitotoxicity and genetic epistasis

    PMID:26936998

    Open questions at the time
    • How Syt10 confers protection mechanistically not fully defined
  11. 2018 Medium

    Defined gene-specific control of excitatory synapse number/strength, showing NPAS4 restricts mossy-fiber-CA3 contacts via Plk2 and scales AMPA receptors via Homer1a.

    Evidence Conditional KO and electrophysiology with Plk2 epistasis; Homer1a promoter reporter, KO and AAV rescue in seizure models

    PMID:29222951 PMID:29429933

    Open questions at the time
    • Whether these pathways operate in the same cells unresolved
    • Homer1a work is largely seizure-context
  12. 2019 High

    Revealed stimulus-specific dimer partitioning — action potentials route NPAS4 to ARNT and EPSPs to ARNT2 — with distinct genome-wide binding, explaining how one factor encodes input identity.

    Evidence Optogenetic AP vs EPSP separation, ChIP-seq of each heterodimer, Co-IP and RNA-seq

    PMID:31585079

    Open questions at the time
    • Molecular sensor distinguishing AP- vs EPSP-derived signals unresolved
    • Downstream phenotypic divergence of the two programs not fully mapped
  13. 2021 Medium

    Extended NPAS4 effector logic to ischemic neuroprotection via Gem-mediated suppression of L-type VGCCs and to interneuron-specific synapse control via IQSEC3 ARF-GEF activity.

    Evidence KO/overexpression in MCAO/OGD with Gem epistasis; SST-specific KO with IQSEC3 dominant-negative rescue

    PMID:34289353 PMID:34349016

    Open questions at the time
    • Whether Gem and Syt10 protection pathways converge unknown
    • Cell-type restriction of IQSEC3 program incompletely mapped
  14. 2021 High

    Broadened NPAS4's systems roles to circadian light response in the SCN and to striatal reward circuitry, with calcium/calcineurin-gated induction in MSNs.

    Evidence SCN multi-omics and circadian behavior in Npas4 KO; calcium imaging, pharmacology, KD, RNA-seq and electrophysiology in NAc/MSNs

    PMID:34416169 PMID:34661342

    Open questions at the time
    • SCN target genes mediating period/phase effects only partly defined
    • Signaling specificity for calcium over PKA mechanistically incomplete
  15. 2022 High

    Provided atomic-resolution structures of NPAS4-ARNT and NPAS4-ARNT2 on DNA, defining an interconnected NPAS4 conformation, partner-specific PAS-A interfaces, and ligand-accessible PAS-B pockets.

    Evidence X-ray crystallography of both heterodimers with biochemical and cell-based reporter validation

    PMID:36343253

    Open questions at the time
    • Identity of any physiological PAS-B ligand unknown
    • Structural basis of differential genomic targeting not directly shown
  16. 2023 High

    Uncovered a non-transcription-factor role: NPAS4 assembles a NuA4-TIP60 complex that recruits DNA repair machinery to recurrently damaged regulatory elements, coupling neuronal activity to genome stability and lifespan.

    Evidence Complex purification from brain, ChIP-seq at damaged elements, DSB mapping, loss-of-function and lifespan assays

    PMID:36792830

    Open questions at the time
    • How NPAS4 recognizes recurrently damaged loci unresolved
    • Relationship between the TF and chromatin-repair roles at shared loci unclear
  17. 2013 Medium

    Mapped the upstream regulation gating NPAS4 induction, showing stress/glucocorticoid receptor binding to negative GREs and REST/CTCF silencing plus miRNA targeting restrain its expression.

    Evidence ChIP, promoter mutagenesis, adrenalectomy and mifepristone in vivo; ChIP and 3'UTR reporter assays with miR-203/miR-224

    PMID:23020797 PMID:24291638

    Open questions at the time
    • Integration of multiple repressive inputs at the locus not unified
    • Functional weight of each input in vivo unquantified
  18. 2017 Medium

    Defined activity-sensitive chromatin gating of Npas4 by class IIa/I HDACs, with HDAC5 in NAc and HDAC3 in dying neurons repressing the Npas4 enhancer/promoter to shape reward and survival outcomes.

    Evidence ChIP at Npas4 regulatory regions, conditional KO/overexpression, HDAC inhibitors and behavioral assays

    PMID:28957664 PMID:31883511

    Open questions at the time
    • Signals controlling HDAC dephosphorylation/recruitment incompletely defined
  19. 2024 Medium

    Tied NPAS4 dynamics to adaptive behavior, showing biphasic NMDAR-dependent Npas4 expression restricts fear memory and promotes extinction via CCK interneuron input.

    Evidence Pharmacological NMDAR/dopamine blockade, genetic manipulation, fear conditioning, immunofluorescence and electrophysiology

    PMID:38347124

    Open questions at the time
    • Molecular basis of biphasic kinetics unresolved
    • Target genes for extinction effect not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown what endogenous ligand, if any, occupies the conserved PAS-B pockets and whether such ligands gate NPAS4 dimer choice or genomic targeting in vivo.
  • No ligand identified for any NPAS4 PAS pocket
  • Mechanism selecting ARNT vs ARNT2 by stimulus not molecularly defined
  • How NPAS4's TF and chromatin-repair functions are coordinated at shared loci unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 1 R-HSA-73894 DNA Repair 1 R-HSA-9909396 Circadian clock 1
Partners
ARNTARNT2ARNTL
Complex memberships
NPAS4-ARNT heterodimerNPAS4-ARNT2 heterodimerNPAS4-NuA4 (TIP60) complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 NPAS4 regulates the expression of activity-dependent genes that control the number of GABA-releasing synapses forming on excitatory neurons, thereby playing a role in activity-dependent development of inhibitory synapses and homeostatic balance between synaptic excitation and inhibition. Loss-of-function (knockout/knockdown) in neurons with inhibitory synapse number as readout; activity-dependent gene expression analysis Nature High 18815592
2004 NPAS4 (LE-PAS) is a nuclear bHLH-PAS transcription factor that heterodimerizes with ARNT (Arnt1) in an Arnt-dependent manner and transactivates the CNS midline enhancer (CME) motif but not the xenobiotic response element, without requiring prior activation of the NPAS4 protein itself. In vitro overexpression in COS-7 cells; reporter gene assay; nuclear localization by cellular fractionation Brain research. Molecular brain research Medium 15363889
2007 NPAS4 (NXF) is a transcriptional activator that associates with the bHLH-PAS co-factor ARNT2 to drive target gene expression; sustained expression of NPAS4 is detrimental (causes cell death and directly activates the Bax gene), whereas endogenous NPAS4 is required for optimal neuroprotection by preconditioning. Reporter assays for transcriptional activation; adenovirus-mediated overexpression; RNA interference knockdown in F-11 cells with neuroprotection readout Brain research Medium 17214977
2008 NPAS4 (NXF) forms functional heterodimers with ARNT1 and ARNT2 in vivo in the brain; co-immunoprecipitation of whole brain extracts with anti-NXF antibody co-precipitated predominantly Arnt2 and detectably Arnt1; in vitro co-precipitation and yeast two-hybrid confirmed direct physical associations; both Arnt1:NXF and Arnt2:NXF heterodimers showed comparable transcriptional activity in reporter assays. Co-immunoprecipitation from whole brain extracts; in vitro co-precipitation with recombinant proteins; yeast two-hybrid; reporter gene assay Biochimica et biophysica acta High 19284974
2011 NPAS4 regulates a transcriptional program in the hippocampal CA3 region required for contextual memory formation; Npas4 recruits RNA Polymerase II to promoters and enhancers of target genes including many well-known activity-regulated genes; selective deletion of Npas4 in CA3 impaired contextual memory, and restoration of Npas4 in CA3 reversed the deficit. Global and region-selective knockout; viral vector-mediated restoration; chromatin immunoprecipitation (ChIP) for RNA Pol II at target gene promoters/enhancers; contextual fear memory behavioral assay Science High 22194569
2013 NPAS4 drives the redistribution of inhibitory synapses on CA1 pyramidal neurons in vivo: behaviourally driven NPAS4 expression simultaneously increases inhibitory synapse number on the cell soma while decreasing them on apical dendrites; BDNF (a direct NPAS4 target gene) specifically mediates somatic but not dendritic inhibition downstream of NPAS4. In vivo mouse hippocampus experiments with NPAS4 loss-of-function; immunohistochemical quantification of inhibitory synapse markers on soma vs. dendrites; epistasis with Bdnf Nature High 24201284
2014 NPAS4 activates distinct programs of late-response genes in inhibitory versus excitatory neurons in response to neuronal activity; in excitatory neurons it promotes inhibitory synapse formation onto them, while in inhibitory neurons it promotes excitatory input onto them, demonstrating cell-type-specific transcriptional programs. Cell-type-specific NPAS4 loss-of-function (conditional KO); RNA-seq; electrophysiology to measure synaptic input changes Cell High 24855953
2009 NPAS4 (NXF) heterodimerizes with ARNT1 and ARNT2 in vivo in the brain, with ARNT2 being the predominant partner detected by co-immunoprecipitation from whole brain extracts. Co-immunoprecipitation from whole brain extracts; in vitro co-precipitation; yeast two-hybrid Biochimica et biophysica acta High 19284974
2012 NPAS4 overexpression increases CDK5-dependent synapsin I phosphorylation in Neuro2a cells and primary hippocampal neurons; NPAS4 binds to the promoters of Cdk5 and NeuN genes as shown by chromatin immunoprecipitation; loss of Npas4 abolishes depolarization-induced neurite outgrowth; in vivo, Npas4 KO mice show no increase in phosphorylated synapsin I after PTZ-induced convulsions. Overexpression and knockdown in Neuro2a cells; primary cultured hippocampal neurons from Npas4 KO mice; ChIP assay for Cdk5/NeuN promoters; CDK5 inhibitor (roscovitine) pharmacology; in vivo PTZ model with Npas4 KO The Journal of biological chemistry Medium 23172225
2013 NPAS4 in pancreatic β-cells directly inhibits the insulin promoter and blocks GLP-1 potentiating effects; NPAS4 protein is degraded via the ubiquitin-proteasome pathway; NPAS4 is induced by classical ER stressors (thapsigargin, palmitate) and prevents ER stress-induced β-cell dysfunction and death. Insulin promoter reporter assays in MIN6 cells; overexpression and loss-of-function; proteasome inhibitor (MG132) treatment; in vivo glucose infusions; human islet studies Diabetes Medium 23656887
2013 NPAS4 expression is repressed by REST/NRSF in embryonic stem cells and non-neuronal cells via binding to multiple sites in the NPAS4 promoter and Intron I; CTCF binding within Intron I also correlates with REST-mediated repression; the 3'UTR of NPAS4 is targeted by miR-203 and miR-224 to post-transcriptionally regulate its expression. Chromatin immunoprecipitation (ChIP) for REST and CTCF at the NPAS4 locus; 3'UTR reporter assays; overexpression of miR-203 and miR-224 Biochimica et biophysica acta Medium 24291638
2014 NPAS4 transcriptional activity requires heterodimerization with ARNT2; human variants NPAS4-F147S and NPAS4-E257K significantly reduce transcriptional activity, with F147S specifically impairing ARNT2 dimerization and BDNF target gene activation; ARNT2-R46W disrupts nuclear localization; the F147 residue lies at the dimer interface as predicted by homology modelling. Luciferase reporter gene assay with human variants; co-immunoprecipitation for ARNT2 dimerization; endogenous BDNF expression assay; nuclear localization microscopy; homology modelling PloS one Medium 24465693
2013 NPAS4 expression is transcriptionally suppressed by stress via glucocorticoid receptor (GR) binding to negative glucocorticoid response elements (nGREs) located -2000 to -1000 upstream of the Npas4 transcription start site; chromatin immunoprecipitation confirmed increased GR binding to the Npas4 promoter in the hippocampus following restraint stress; adrenalectomy increased Npas4 expression. Chromatin immunoprecipitation (ChIP) in hippocampus after restraint stress; promoter mutagenesis; GR antagonist (mifepristone) treatment; adrenalectomy Journal of neurochemistry Medium 23020797
2014 NPAS4 regulates Mdm2 expression to control ubiquitination and degradation of the microtubule-associated protein Dcx, thereby regulating dendritic spine development in newborn olfactory bulb granule cells after sensory experience. NPAS4 overexpression and KO in olfactory bulb granule cells; loss-of-function of Mdm2; measurement of Dcx ubiquitination; dendritic spine density quantification Cell reports Medium 25088421
2015 NPAS4 mRNA and protein have high turnover rates; at the protein level, NPAS4 is degraded via the ubiquitin-proteasome pathway; NPAS4 expression in pancreatic β-cells is regulated by calcineurin, Akt/PKB, and CaMK signaling pathways. Pharmacological inhibition of calcineurin, Akt, and CaMK; proteasome inhibitor treatment; measurement of NPAS4 mRNA and protein turnover rates in MIN6 cells and mouse islets The Journal of biological chemistry Medium 26663079
2015 Chronic restraint stress increases DNA methylation of two CpG islands in the Npas4 promoter; methylation of CpG island 2, which overlaps with cAMP response element (CRE) sequences, reduces Npas4 promoter activity; treatment with a DNA methyltransferase inhibitor (5-aza-2'-deoxycytidine) increases Npas4 mRNA levels. Bisulfite sequencing of CpG islands in hippocampus after restraint stress; DNA methyltransferase inhibitor treatment; Npas4 promoter-CRE mutagenesis reporter assay in Neuro2a cells Neuroreport Medium 26222956
2017 NPAS4 controls a homeostatic scaling mechanism in hippocampal CA3 neurons via Homer1a: seizure activity upregulates NPAS4, which increases Homer1a promoter activity; in Npas4 KO mice, seizure-induced Homer1a induction is attenuated; NPAS4-Homer1a signaling mediates downregulation of postsynaptic AMPA receptors (GluA1 subunit) to reduce excitatory synaptic transmission. Reporter assay for Homer1a promoter activity; Npas4 KO mice with PTZ-induced seizures; AAV-Homer1a rescue in Npas4 KO; electrophysiology of CA3 synapses; immunofluorescence co-localization Journal of neurochemistry Medium 29222951
2017 HDAC5 in nucleus accumbens directly associates with an activity-sensitive enhancer of the Npas4 gene and negatively regulates NPAS4 expression; dephosphorylated nuclear HDAC5 reduces NPAS4 expression and thereby reduces cocaine reward-context associations. ChIP for HDAC5 at the Npas4 enhancer; conditional deletion of Npas4 in the NAc; cocaine self-administration behavioral assays Neuron Medium 28957664
2018 NPAS4 selectively regulates the structure and strength of mossy fiber-CA3 synapses by restricting functional synaptic contact number without affecting other CA3 inputs; NPAS4 exerts this effect by controlling expression of the polo-like kinase Plk2. Npas4 conditional KO in CA3; activity-dependent reporter to identify learning-activated cells; electrophysiology of MF-CA3 synapses; genetic epistasis with Plk2 Neuron Medium 29429933
2018 Novel sensory experience selectively enhances somatic inhibition mediated by cholecystokinin-expressing basket cells (CCKBCs) in an NPAS4-dependent manner; NPAS4 increases the number of CCKBC-to-PN synapses specifically and enhances cannabinoid-mediated plasticity (DSI) at these synapses. In vivo sensory experience protocol; NPAS4 loss-of-function (KO); electrophysiology measuring CCKBC-mediated IPSCs; synapse counting by immunofluorescence eLife Medium 30052197
2018 NPAS4 possesses multiple nuclear localization signals (NLS) and nuclear export signals (NES) distributed across its bHLH domain, PAS-2 domain, and C-terminus; cytoplasmic localization of NPAS4 is leptomycin B-sensitive, indicating CRM1-dependent nuclear export; glucose concentration influences NPAS4 subcellular localization. Subcellular fractionation and fluorescence microscopy in COS-7 and N2a cells; leptomycin B treatment; deletion/mutation constructs to map NLS/NES sequences The Journal of biological chemistry Medium 29899116
2019 Action potentials (APs) and excitatory postsynaptic potentials (EPSPs) trigger two spatially segregated and molecularly distinct induction mechanisms leading to NPAS4 expression; AP-induced NPAS4 forms heterodimers with ARNT, while EPSP-induced NPAS4 forms heterodimers with ARNT2; these two stimulus-specific NPAS4 heterodimers exhibit distinct DNA binding patterns across the genome. Optogenetic stimulation to separate AP vs EPSP inputs in hippocampal neurons; ChIP-seq for NPAS4-ARNT and NPAS4-ARNT2 heterodimers; co-immunoprecipitation to identify heterodimer identity; RNA-seq Cell High 31585079
2013 NPAS4 (NXF/Nxf) is required for optimal neuroprotection by neuronal preconditioning; it is a transcriptional activator associating with ARNT2; in vivo, NXF knockout mice show age-dependent neurodegeneration and increased susceptibility to glutamate excitotoxicity. NXF knockout mice generated by homologous recombination; glutamate excitotoxicity model; histological analysis of neurodegeneration; reporter assays for transcriptional activity The Journal of biological chemistry Medium 19001414
2016 NPAS4 is required for neuroprotection against excitotoxic insults; synaptotagmin 10 (Syt10) is identified as a direct neuroprotective effector downstream of NPAS4: NPAS4 is critical for activity-induced upregulation of Syt10 expression, and NPAS4's ability to confer neuroprotection against kainate-induced excitotoxicity is severely diminished in Syt10 KO neurons. Syt10 KO neurons; NPAS4 KO/overexpression; kainic acid excitotoxicity model; genetic epistasis between NPAS4 and Syt10 The Journal of neuroscience Medium 26936998
2013 NPAS4 forms functional dimers with ARNT, ARNT2, and ARNTL in the ovine pars tuberalis; NPAS4-ARNT transactivation of the Cry1 promoter is codependent upon two conserved central midline elements (CMEs); Npas4 is a rapidly induced immediate early gene in PT cells in response to melatonin and drives expression of clock genes Cry1 and Nampt. In vitro dimerization assay; reporter gene assay with 5'-deletions and site-directed mutagenesis of the Cry1 promoter; in vivo nuclear localization by immunohistochemistry; in situ hybridization for acute Npas4 induction by melatonin Molecular endocrinology Medium 23598442
2021 NPAS4 regulates circadian behavior by controlling the transcriptional response of the SCN to light; Npas4 KO mice show longer circadian period under constant conditions, a damped phase response curve to light, and reduced light-induced gene expression in the SCN; NPAS4 target genes are enriched in light-responsive SCN cell types (AVP, VIP, CCK neurons). RNA-seq, ChIP-seq, and single-nucleus sequencing of SCN; Npas4 KO mice; circadian behavioral assays (free-running period, phase response curve) Neuron High 34416169
2021 NPAS4 in medium spiny neurons (MSNs) is induced by synaptic stimuli causing calcium influx but not by dopaminergic or PKA-stimulating input; this induction depends on calcineurin and nuclear calcium signaling rather than PKA or MAPK cascades; NPAS4 controls MSN spine density, firing rate, and I/O gain function, and determines cocaine-induced hyperlocomotion. Calcium imaging; pharmacological pathway dissection (calcineurin inhibitor, PKA inhibitor, MAPK inhibitor); Npas4 knockdown in NAc; RNA-seq for NPAS4 regulon; electrophysiology (firing rate, I/O gain, paired-pulse facilitation); human iPSC-derived forebrain organoids EMBO reports Medium 34661342
2021 NPAS4 transcriptionally upregulates IQSEC3 (an ARF-GEF at GABAergic synapses) specifically in CA1 stratum oriens somatostatin (SST)-expressing interneurons after enriched environment exposure; SST-specific Npas4 KO reduces GABAergic synaptic transmission in these interneurons and increases CA1 pyramidal neuron activity; rescue by wild-type but not ARF-GEF-inactive IQSEC3 confirms ARF activity is required downstream. SST interneuron-specific conditional Npas4 KO (Cre-lox); electrophysiology; ARF-GEF dominant-negative rescue; behavioral anxiety assays; immunofluorescence for IQSEC3 in SST interneurons Cell reports Medium 34289353
2021 NPAS4 neuroprotection in ischemia involves activation of the Gem gene (encoding a Ras-related GTPase); Gem suppresses membrane localization of L-type voltage-gated Ca2+ channels (VGCCs) to inhibit excess Ca2+ influx, protecting neurons from excitotoxic death; Npas4 is necessary and sufficient for neuroprotection in MCAO and OGD models. Npas4 KO and overexpression in MCAO in vivo and OGD in vitro; systematic search for Npas4-downstream genes; Gem overexpression/knockdown; measurement of L-type VGCC membrane localization; human cerebral organoid ischemia model Proceedings of the National Academy of Sciences of the United States of America Medium 34349016
2022 Crystal structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers in complex with DNA revealed a uniquely interconnected domain conformation for NPAS4; the PAS-A domains of ARNT and ARNT2 adopt variable conformations in the two heterodimers; ARNT PAS-A forms a distinct interface with both PAS-A and PAS-B domains of NPAS4, different from other ARNT heterodimers; the PAS-B domains of NPAS4, ARNT, and ARNT2 all contain ligand-accessible pockets. X-ray crystallography of NPAS4-ARNT and NPAS4-ARNT2 heterodimers; biochemical validation; cell-based reporter assays Proceedings of the National Academy of Sciences of the United States of America High 36343253
2023 NPAS4 assembles a new form of the NuA4-TIP60 chromatin modifier complex (NPAS4-NuA4) in activated neurons; this complex binds recurrently damaged regulatory elements in the brain, recruits DNA repair machinery to stimulate repair of activity-induced DNA double-strand breaks, and partially protects gene regulatory elements against age-dependent somatic mutation accumulation; impaired NPAS4-NuA4 leads to dysregulated activity-dependent transcription, loss of inhibitory control, genome instability, and reduced organismal lifespan. Complex purification from brain; ChIP-seq for NPAS4-NuA4 at damaged regulatory elements; characterization of activity-induced DNA double-strand break landscape; loss-of-function of NPAS4-NuA4 components; lifespan assays Nature High 36792830
2023 NPAS4 in the medial prefrontal cortex is required for chronic social defeat stress-induced reductions in pyramidal neuron dendritic spine density and excitatory synaptic transmission, and for expression of anhedonia-like behavior; NPAS4 is not required for CSDS-induced social avoidance or anxiety-like behavior; NPAS4 regulates expression of genes linked to glutamatergic synapses and ribosomal function. mPFC-specific Npas4 loss-of-function; dendritic spine density quantification; electrophysiology (excitatory synaptic transmission, presynaptic function); sucrose preference and natural reward behavioral assays; RNA-seq of mPFC tissue eLife Medium 36780219
2021 NPAS4 transcriptionally regulates NLRP6 by binding to the Nlrp6 promoter region (-400 to -391 bp and -33 to -24 bp); NPAS4 knockdown reduces pyroptosis markers (cleaved Caspase-1, cleaved Caspase-11, N-terminal GSDMD) and MPO-positive cells after intracerebral hemorrhage; NPAS4 overexpression reverses these effects. ChIP demonstrating NPAS4 binding to Nlrp6 promoter; NPAS4 knockdown and overexpression in ICH mouse model; measurement of pyroptosis markers by Western blot and immunofluorescence International journal of molecular sciences Medium 37176030
2023 NPAS4 in the NAc is required for cocaine conditioned place preference; NPAS4 functions specifically within D2-class (not D1-class) MSNs to support cocaine-context associations and cue-induced cocaine seeking, by suppressing drug-induced counteradaptations that oppose relapse. Conditional Npas4 deletion in D1- vs D2-MSNs; cocaine CPP and cue-induced seeking behavioral assays; viral vector strategies in mice Nature communications Medium 39117647
2021 Loss-of-function variants in NPAS4 that truncate the protein result in complete loss of transcriptional activity due to inability to heterodimerize with ARNT2, as confirmed by co-immunoprecipitation. Reporter gene activity assay with NPAS3/4 variants; co-immunoprecipitation with ARNT2 Scientific reports Medium 33758288
2019 HDAC3 associates with the Npas4 promoter specifically in neurons primed to die (not healthy neurons); overexpression of HDAC3 suppresses Npas4 and Bdnf expression in cortical neurons; HDAC3 inhibition (RGFP966) upregulates Npas4 expression; HDAC3 represses Npas4 promoter activity. ChIP-seq followed by ChIP confirmation for HDAC3 at Npas4 promoter; HDAC3 overexpression; HDAC3 inhibitor (RGFP966) treatment; Npas4 promoter reporter assay BMC neuroscience Medium 31883511
2022 NPAS4 expression in SST interneurons is selectively induced during motor learning in M1; cell-type-specific deletion of Npas4 in M1 disrupts learning-induced dendritic spine reorganization in pyramidal neurons and impairs motor learning; NPAS4-expressing SST-INs show lower activity during task-related movements; chemogenetically increasing activity of NPAS4-expressing ensembles mimics Npas4 deletion effects. Two-photon in vivo imaging of dendritic spines; SST-specific Npas4 conditional KO; motor learning behavioral assays; chemogenetic activation (DREADD) of NPAS4-expressing SST-INs Neuron Medium 36099920
2024 High-salience learning induces a biphasic Npas4 expression in the hippocampus; the late phase requires NMDA receptor activity and is independent of dopaminergic neurotransmission; this biphasic Npas4 expression restricts fear memory consolidation and promotes behavioral flexibility by facilitating fear extinction, mediated in part by increased synaptic input from CCK-expressing interneurons. In vivo pharmacological manipulation (NMDA receptor blockade, dopamine receptor blockade); Npas4 genetic manipulation; contextual fear conditioning behavioral assay; immunofluorescence for CCK interneuron synapses; electrophysiology Molecular psychiatry Medium 38347124
2023 NPAS4 mediates dopamine receptor D4 (Drd4) synthesis in neurons of the lateral-to-anterior basal amygdala pathway; Npas4-mediated Drd4 expression gates fear expression toward unpaired conditioned stimuli (CS-) to support safety memory consolidation; this process is blocked by stress/corticosterone. Genetic epistasis between Npas4 and Drd4; Npas4 KO and Drd4 KO; fear conditioning behavioral assays; corticosterone injection; electrophysiology of LA-BA pathway Cell reports Medium 37379214
2021 CGRP impairs fear memory by increasing Npas4 expression via the PKD/phospho-HDAC5 pathway; CGRP decreases HDAC5 binding to the Npas4 enhancer site and increases acetylated histone H3 binding to the Npas4 enhancer; PKD inhibition or knockdown attenuates both CGRP-mediated fear memory impairment and Npas4 induction. Intracerebroventricular CGRP administration; ChIP for HDAC5 and acetylated histone H3 at Npas4 enhancer; PKD pharmacological inhibition and knockdown; Npas4 knockdown; contextual fear memory behavioral assay Scientific reports Medium 33772088

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Activity-dependent regulation of inhibitory synapse development by Npas4. Nature 518 18815592
2014 Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs. Cell 328 24855953
2011 Npas4 regulates a transcriptional program in CA3 required for contextual memory formation. Science (New York, N.Y.) 248 22194569
2013 The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition. Nature 239 24201284
2016 Npas4: Linking Neuronal Activity to Memory. Trends in neurosciences 160 26987258
2010 Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice: possible involvement of a brain-specific transcription factor Npas4. Journal of neurochemistry 122 20626564
2017 HDAC5 and Its Target Gene, Npas4, Function in the Nucleus Accumbens to Regulate Cocaine-Conditioned Behaviors. Neuron 98 28957664
2012 Npas4: a neuronal transcription factor with a key role in social and cognitive functions relevant to developmental disorders. PloS one 98 23029555
2023 A NPAS4-NuA4 complex couples synaptic activity to DNA repair. Nature 93 36792830
2000 The mRNA export in Caenorhabditis elegans is mediated by Ce-NXF-1, an ortholog of human TAP/NXF and Saccharomyces cerevisiae Mex67p. RNA (New York, N.Y.) 90 11142376
2018 Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation. Neuron 80 29429933
2011 The neuronal PAS domain protein 4 (Npas4) is required for new and reactivated fear memories. PloS one 80 21887312
2021 NPAS4 regulates the transcriptional response of the suprachiasmatic nucleus to light and circadian behavior. Neuron 75 34416169
2006 Npas4, a novel helix-loop-helix PAS domain protein, is regulated in response to cerebral ischemia. The European journal of neuroscience 58 17156197
2020 Essential Functions of the Transcription Factor Npas4 in Neural Circuit Development, Plasticity, and Diseases. Frontiers in neuroscience 57 33335473
2012 Experience-dependent expression of NPAS4 regulates plasticity in adult visual cortex. The Journal of physiology 57 22674715
2011 Developmental influence of the serotonin transporter on the expression of npas4 and GABAergic markers: modulation by antidepressant treatment. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 56 22012473
2019 Genomic Decoding of Neuronal Depolarization by Stimulus-Specific NPAS4 Heterodimers. Cell 55 31585079
2017 Differential expression of the immediate early genes c-Fos, Arc, Egr-1, and Npas4 during long-term memory formation in the context preexposure facilitation effect (CPFE). Neurobiology of learning and memory 52 29222058
2001 Small bristles, the Drosophila ortholog of NXF-1, is essential for mRNA export throughout development. RNA (New York, N.Y.) 49 11780634
2013 Increased cell-intrinsic excitability induces synaptic changes in new neurons in the adult dentate gyrus that require Npas4. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 23637184
2014 Npas4 regulates Mdm2 and thus Dcx in experience-dependent dendritic spine development of newborn olfactory bulb interneurons. Cell reports 45 25088421
2004 Nxf and Fbxo33: novel seizure-responsive genes in mice. The European journal of neuroscience 43 15380003
2018 NPAS4 recruits CCK basket cell synapses and enhances cannabinoid-sensitive inhibition in the mouse hippocampus. eLife 41 30052197
2016 Identification of Synaptotagmin 10 as Effector of NPAS4-Mediated Protection from Excitotoxic Neurodegeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 26936998
2015 The Role of the Neuroprotective Factor Npas4 in Cerebral Ischemia. International journal of molecular sciences 41 26690124
2020 Reversal of synaptic and behavioral deficits in a 16p11.2 duplication mouse model via restoration of the GABA synapse regulator Npas4. Molecular psychiatry 40 32099100
2013 Npas4 is a novel activity-regulated cytoprotective factor in pancreatic β-cells. Diabetes 38 23656887
2015 Reduction of the neuroprotective transcription factor Npas4 results in increased neuronal necrosis, inflammation and brain lesion size following ischaemia. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 37 26661154
2014 Effects of Npas4 deficiency on anxiety, depression-like, cognition and sociability behaviour. Behavioural brain research 37 25549857
2004 NXF-2, REF-1, and REF-2 affect the choice of nuclear export pathway for tra-2 mRNA in C. elegans. Molecular cell 37 15175155
2004 LE-PAS, a novel Arnt-dependent HLH-PAS protein, is expressed in limbic tissues and transactivates the CNS midline enhancer element. Brain research. Molecular brain research 37 15363889
2015 Npas4 Transcription Factor Expression Is Regulated by Calcium Signaling Pathways and Prevents Tacrolimus-induced Cytotoxicity in Pancreatic Beta Cells. The Journal of biological chemistry 36 26663079
2012 Neuronal Per Arnt Sim (PAS) domain protein 4 (NPAS4) regulates neurite outgrowth and phosphorylation of synapsin I. The Journal of biological chemistry 36 23172225
2008 Functional characterization of basic helix-loop-helix-PAS type transcription factor NXF in vivo: putative involvement in an "on demand" neuroprotection system. The Journal of biological chemistry 36 19001414
2013 Regulation of the neuronal transcription factor NPAS4 by REST and microRNAs. Biochimica et biophysica acta 35 24291638
2019 Environmental enrichment improves pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain: role of NPAS4. Psychopharmacology 33 30798405
2005 Molecular cloning and functional characterization of mouse Nxf family gene products. Genomics 33 15820316
2012 Transcriptional suppression of the neuronal PAS domain 4 (Npas4) gene by stress via the binding of agonist-bound glucocorticoid receptor to its promoter. Journal of neurochemistry 31 23020797
2013 Activity-dependent NPAS4 expression and the regulation of gene programs underlying plasticity in the central nervous system. Neural plasticity 30 24024041
2022 Functionally distinct NPAS4-expressing somatostatin interneuron ensembles critical for motor skill learning. Neuron 29 36099920
2022 Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family. Proceedings of the National Academy of Sciences of the United States of America 29 36343253
2017 Neuronal PAS domain protein 4 (Npas4) controls neuronal homeostasis in pentylenetetrazole-induced epilepsy through the induction of Homer1a. Journal of neurochemistry 29 29222951
2020 Amyloid Precursor Protein (APP) Controls the Expression of the Transcriptional Activator Neuronal PAS Domain Protein 4 (NPAS4) and Synaptic GABA Release. eNeuro 28 32327470
2013 Npas4 is activated by melatonin, and drives the clock gene Cry1 in the ovine pars tuberalis. Molecular endocrinology (Baltimore, Md.) 28 23598442
2005 Identification and characterization of the mouse nuclear export factor (Nxf) family members. Nucleic acids research 28 16027110
2023 NPAS4 in the medial prefrontal cortex mediates chronic social defeat stress-induced anhedonia-like behavior and reductions in excitatory synapses. eLife 27 36780219
2021 RyR-mediated Ca2+ release elicited by neuronal activity induces nuclear Ca2+ signals, CREB phosphorylation, and Npas4/RyR2 expression. Proceedings of the National Academy of Sciences of the United States of America 27 34389673
2021 Npas4 regulates medium spiny neuron physiology and gates cocaine-induced hyperlocomotion. EMBO reports 27 34661342
2018 Npas4 deficiency interacts with adolescent stress to disrupt prefrontal GABAergic maturation and adult cognitive flexibility. Genes, brain, and behavior 25 29345055
2022 Empagliflozin enhances neuroplasticity in rotenone-induced parkinsonism: Role of BDNF, CREB and Npas4. Life sciences 24 36462721
2019 Downregulation of Npas4 in parvalbumin interneurons and cognitive deficits after neonatal NMDA receptor blockade: relevance for schizophrenia. Translational psychiatry 24 30792384
2016 Decreased Npas4 and Arc mRNA Levels in the Hippocampus of Aged Memory-Impaired Wild-Type But Not Memory Preserved 11β-HSD1 Deficient Mice. Journal of neuroendocrinology 24 26563879
2013 Repeated aripiprazole treatment regulates Bdnf, Arc and Npas4 expression under basal condition as well as after an acute swim stress in the rat brain. Pharmacological research 24 24309096
2007 Transient expression of Nxf, a bHLH-PAS transactivator induced by neuronal preconditioning, confers neuroprotection in cultured cells. Brain research 24 17214977
2015 Npas4 deficiency increases vulnerability to juvenile stress in mice. Behavioural brain research 23 25911220
2012 Identification of optogenetically activated striatal medium spiny neurons by Npas4 expression. PloS one 23 23300775
2021 Npas4 regulates IQSEC3 expression in hippocampal somatostatin interneurons to mediate anxiety-like behavior. Cell reports 21 34289353
2018 Npas4 deficiency and prenatal stress interact to affect social recognition in mice. Genes, brain, and behavior 21 29227584
2014 Human variants in the neuronal basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function. PloS one 21 24465693
2009 Characterization of functional heterodimer partners in brain for a bHLH-PAS factor NXF. Biochimica et biophysica acta 21 19284974
2016 The transcription factor Npas4 contributes to adolescent development of prefrontal inhibitory circuits, and to cognitive and emotional functions: Implications for neuropsychiatric disorders. Neurobiology of disease 18 27993645
2019 The Bdnf and Npas4 genes are targets of HDAC3-mediated transcriptional repression. BMC neuroscience 17 31883511
2015 NPAS4 Facilitates the Autophagic Clearance of Endogenous Tau in Rat Cortical Neurons. Journal of molecular neuroscience : MN 17 26635026
2013 Upregulation of the neuronal Per-Arnt-Sim domain protein 4 (Npas4) in the rat corticolimbic system following focal cerebral ischemia. The European journal of neuroscience 17 23431968
2021 NPAS4 suppresses propofol-induced neurotoxicity by inhibiting autophagy in hippocampal neuronal cells. Archives of biochemistry and biophysics 16 34418347
2024 Biphasic Npas4 expression promotes inhibitory plasticity and suppression of fear memory consolidation in mice. Molecular psychiatry 15 38347124
2021 Neuroprotective Effects Against Cerebral Ischemic Injury Exerted by Dexmedetomidine via the HDAC5/NPAS4/MDM2/PSD-95 Axis. Molecular neurobiology 15 33411316
2021 Ras-like Gem GTPase induced by Npas4 promotes activity-dependent neuronal tolerance for ischemic stroke. Proceedings of the National Academy of Sciences of the United States of America 15 34349016
2017 The neuronal transcription factor NPAS4 is a strong inducer of sprouting angiogenesis and tip cell formation. Cardiovascular research 15 28082451
2014 The inhibitory effects of Npas4 on seizures in pilocarpine-induced epileptic rats. PloS one 15 25536221
2017 Stress-induced hippocampus Npas4 mRNA expression relates to specific psychophysiological patterns of stress response. Brain research 14 29196218
2014 A reduction in Npas4 expression results in delayed neural differentiation of mouse embryonic stem cells. Stem cell research & therapy 14 24887558
2016 miR-744 and miR-224 Downregulate Npas4 and Affect Lineage Differentiation Potential and Neurite Development During Neural Differentiation of Mouse Embryonic Stem Cells. Molecular neurobiology 13 27189618
2015 Stress increases DNA methylation of the neuronal PAS domain 4 (Npas4) gene. Neuroreport 13 26222956
2011 De novo duplication of Xq22.1→q24 with a disruption of the NXF gene cluster in a mentally retarded woman with short stature and premature ovarian failure. Taiwanese journal of obstetrics & gynecology 13 22030050
2021 Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice. Scientific reports 12 33772088
2016 Alterations in anxiety and social behaviour in Npas4 deficient mice following photochemically-induced focal cortical stroke. Behavioural brain research 12 27574128
2024 NPAS4 supports cocaine-conditioned cues in rodents by controlling the cell type-specific activation balance in the nucleus accumbens. Nature communications 11 39117647
2021 Molecular characterisation of rare loss-of-function NPAS3 and NPAS4 variants identified in individuals with neurodevelopmental disorders. Scientific reports 10 33758288
2020 Maternal Separation Early in Life Alters the Expression of Genes Npas4 and Nr1d1 in Adult Female Mice: Correlation with Social Behavior. Behavioural neurology 10 32190129
2018 Multiple sequences orchestrate subcellular trafficking of neuronal PAS domain-containing protein 4 (NPAS4). The Journal of biological chemistry 10 29899116
2017 RNA-binding proteins of the NXF (nuclear export factor) family and their connection with the cytoskeleton. Cytoskeleton (Hoboken, N.J.) 10 28296067
2023 Npas4-mediated dopaminergic regulation of safety memory consolidation. Cell reports 9 37379214
2023 Downregulated NPAS4 in multiple brain regions is associated with major depressive disorder. Scientific reports 9 38062059
2022 Differential expression of NPAS4 in the dorsolateral prefrontal cortex following opioid overdose. Drug and alcohol dependence reports 9 36845993
2018 Growth of Triple Negative and Progesterone Positive Breast Cancer Causes Oxidative Stress and Down-Regulates Neuroprotective Transcription Factor NPAS4 and NPAS4-Regulated Genes in Hippocampal Tissues of TumorGraft Mice-an Aging Connection. Frontiers in genetics 9 29556248
2023 NPAS4 Exacerbates Pyroptosis via Transcriptionally Regulating NLRP6 in the Acute Phase of Intracerebral Hemorrhage in Mice. International journal of molecular sciences 8 37176030
2022 Intranasal calcitonin gene-related peptide administration impairs fear memory retention in mice through the PKD/p-HDAC5/Npas4 pathway. Scientific reports 8 35087146
2015 Expression of Npas4 mRNA in Telencephalic Areas of Adult and Postnatal Mouse Brain. Frontiers in neuroanatomy 8 26633966
2025 Empagliflozin Mitigates PTZ-Induced Seizures in Rats: Modulating Npas4 and CREB-BDNF Signaling Pathway. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 7 39776284
2015 Npas4 expression in two experimental models of the barrel cortex plasticity. Neural plasticity 7 25785202
2007 Characterization of Drosophila and Caenorhabditis elegans NXF-like-factors, putative homologs of mammalian NXF. Gene 7 17628356
2024 Protective effects of taurine on heat Stress-Induced cognitive impairment through Npas4 and Lcn2. International immunopharmacology 6 39405930
2021 Profound downregulation of neural transcription factor Npas4 and Nr4a family in fetal mice neurons infected with Zika virus. PLoS neglected tropical diseases 6 34048439
2023 Theanine, a Tea-Leaf-Specific Amino Acid, Alleviates Stress through Modulation of Npas4 Expression in Group-Housed Older Mice. International journal of molecular sciences 4 36835393
2019 Activity-Dependent Transcription Collaborates with Local Dendritic Translation to Encode Stimulus-Specificity in the Genome Binding of NPAS4. Neuron 4 31751544
2018 Structural insights and characterization of human Npas4 protein. PeerJ 4 29915698
2015 Identification of the extent of cortical spreading depression propagation by Npas4 mRNA expression. Neuroscience research 4 25912092
2022 Dysregulation of Npas4 and Inhba expression and an altered excitation-inhibition balance are associated with cognitive deficits in DBA/2 mice. Learning & memory (Cold Spring Harbor, N.Y.) 3 35042829

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