| 1995 |
NPTX2 (neuronal pentraxin II) was identified as a secreted member of the pentraxin family with potential N-linked glycosylation sites, expressed in brain, testis, pancreas, liver, heart, and skeletal muscle. The human gene is 11 kb, contains four introns, and is localized to chromosome 7q21.3-q22.1. |
cDNA cloning, Northern blot analysis, genomic sequencing |
Genomics |
Medium |
8530029
|
| 2017 |
NPTX2 is an activity-dependent immediate early gene expressed presynaptically by pyramidal neurons that regulates excitatory synapses onto parvalbumin (PV) interneurons by controlling AMPA receptor subunit GluA4 expression. In Nptx2-/- mice, GluA4 expression is reduced, network rhythmicity is disrupted, and pyramidal neuron excitability is increased. |
Nptx2 knockout mouse model, electrophysiology, immunohistochemistry, postmortem human cortex analysis |
eLife |
High |
28440221
|
| 2021 |
NPTX2 function requires activity-dependent exocytosis and dynamic shedding at synapses. Behavior-linked NPTX2 trafficking is abolished by mutations that disrupt select activity-dependent plasticity mechanisms of excitatory neurons. NPTX2 loss of function results in failure of parvalbumin interneurons to adaptively respond to behavioral stress. |
Transgenic mouse models with Nptx2 loss of function, activity-dependent trafficking assays, behavioral stress paradigms |
Science advances |
High |
34818031
|
| 2023 |
NPTX2 binds complement C1q and thereby regulates complement activity in the brain. Nptx2-deficient mice show increased complement activity, C1q-dependent microglial synapse engulfment, and loss of excitatory synapses. AAV-mediated neuronal overexpression of Nptx2 was sufficient to restrain complement activity and ameliorate microglia-mediated synapse loss. |
Co-immunoprecipitation (NPTX2-C1q interaction), Nptx2 knockout mouse, AAV overexpression in aged TauP301S mice, complement activity assays, synapse engulfment quantification, CSF analysis of human FTD samples |
Science translational medicine |
High |
36989373
|
| 2024 |
TDP-43 binds the 3' UTR of NPTX2 mRNA to control NPTX2 protein levels. Loss of nuclear TDP-43 function leads to NPTX2 misaccumulation/overexpression, which causes neurotoxicity. Correcting NPTX2 misregulation partially rescues neurons from TDP-43-induced neurodegeneration. |
iPSC-derived neural networks (iNets), single-cell transcriptomics, TDP-43 overexpression causing aggregation, NPTX2 overexpression rescue/toxicity experiments, patient tissue validation (ALS/FTLD) |
Nature |
High |
38355792
|
| 2019 |
NPTX2 interacts physically with frizzled class receptor 6 (FZD6) to promote β-catenin nuclear translocation, activating the Wnt/β-catenin signaling pathway and driving colorectal cancer cell proliferation and metastasis. Knockdown of FZD6 almost completely reversed NPTX2's proliferative effects. |
Co-immunoprecipitation (NPTX2-FZD6 interaction), siRNA knockdown of FZD6, in vitro proliferation/invasion assays, in vivo xenograft, Western blot of β-catenin targets |
Cell death & disease |
Medium |
30833544
|
| 2019 |
In dorsal hippocampus, retrieval-driven upregulation of NPTX2 recruits GluA1-AMPA receptors via its pentraxin (PTX) domain, enhancing excitatory synaptic transmission and facilitating extinction of cocaine-associated context memory. Overexpressing the carboxyl cytoplasmic tail of GluA1 prevented NPTX2-mediated synaptic remodeling. |
Ribosomal tagging translational profiling, electrophysiology, neuronal tracing, doxycycline-dependent activity marking (DRAM system), Nptx2 manipulation in dorsal hippocampus, GluA1 tail overexpression |
Biological psychiatry |
High |
31836174
|
| 2018 |
NPTX2 expression in the adult hippocampus regulates anxiety behavior and hippocampal cell proliferation. Hippocampus-specific (but not amygdala-specific) Nptx2 knockout increased anxiety and altered glucocorticoid receptor target gene expression after acute stress. Overexpression of Nptx2 in hippocampus alleviated stress-induced anxious behaviors. |
Region-specific conditional Nptx2 knockout and overexpression mouse models, behavioral anxiety assays, gene expression analysis of glucocorticoid receptor targets, adult neurogenesis quantification |
Neuropsychopharmacology |
High |
29844474
|
| 2010 |
Ectopic NPTX2 expression in pancreatic cancer cells (PANC-1) promotes G0-G1 arrest and apoptosis (upregulating Bax and downregulating Cyclin D1), and reduces cell proliferation, migration, and invasion. Low endogenous NPTX2 expression in pancreatic cancer cells correlates with promoter hypermethylation, which is reversed by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. |
Stable NPTX2 cDNA transfection in PANC-1 cells, cell cycle analysis, apoptosis assays, methylation-specific PCR, 5-aza-dC treatment, Western blot |
Molecular biology reports |
Medium |
21161403
|
| 2021 |
NPTX2 promotes gastric cancer cell proliferation and inhibits apoptosis and cell cycle arrest by activating the p53 signaling pathway. NPTX2 overexpression enhanced protein expression of p53, p21, and PTEN. NPTX2 promoter hypermethylation causes its downregulation in gastric cancer cells. |
Western blot, colony formation, CCK-8, flow cytometry, methylation-specific PCR |
Bioengineered |
Medium |
33896384
|
| 2021 |
NPTX2 overexpression promotes proliferation, invasion, migration, and tumorigenesis of epithelial ovarian cancer cells via activation of the IL6-JAK2/STAT3 signaling pathway. Hypoxia-inducible factor 1 (HIF-1) promotes NPTX2 transcription under hypoxic conditions. NPTX2 knockdown abolished hypoxia-induced malignant phenotypes. |
Lentiviral overexpression/knockdown in EOC cell lines, MTS assay, EdU assay, transwell assay, luciferase reporter assay, xenograft experiment, Western blot |
Frontiers in oncology |
Medium |
33768003
|
| 2023 |
NPTX2 interacts with METTL3, increases METTL3 expression, and promotes METTL3-mediated N6-methyladenosine (m6A) modification of SNAIL mRNA, thereby facilitating epithelial-mesenchymal transition in cutaneous squamous cell carcinoma. METTL3 knockdown and m6A inhibition reversed NPTX2 overexpression effects. |
Co-immunoprecipitation (NPTX2-METTL3 interaction), lentiviral overexpression/knockdown, Western blot, m6A assays, xenograft experiment |
The Journal of investigative dermatology |
Medium |
36638907
|
| 2025 |
NPTX2 overexpression in lateral entorhinal cortex (LEC) neurons stabilizes excitatory inputs onto fast-spiking inhibitory interneurons (FS-INs), enhancing feedforward inhibition of dentate gyrus granule cells, and improves spatial memory in aged learning-impaired rats. This demonstrates that NPTX2-mediated recruitment of FS-INs is required for maintaining proficient memory. |
AAV-mediated Nptx2 overexpression in LEC, in vivo electrophysiology (feedforward inhibition measurement), spatial memory behavioral testing in aged rats |
Progress in neurobiology |
High |
40057261
|
| 2023 |
NPTX2 KO mice exhibit disrupted circadian onset time, increased activity during the sleep phase, sleep fragmentation, altered power across EEG frequency bands in wake/NREM/REM states, and diminished sleep spindles. These sleep and circadian rhythm disruptions occur despite intact orexin expression, establishing NPTX2 as an independent effector of sleep/circadian regulation. |
Nptx2 KO mice, EEG/EMG sleep recording, circadian activity monitoring, brain orexin immunostaining |
bioRxivpreprint |
Medium |
37808783
|
| 2025 |
In hippocampal dentate gyrus engram cells, NPTX2 facilitates perisomatic inhibition of Npas4+ ensemble neurons by parvalbumin+ interneurons, preventing fear memory overgeneralization. NPTX2 depletion in Npas4+ engram cells causes memory imprecision, and overexpression of the AMPAR-binding domain of NPTX2 in Npas4+ ensembles rescued memory imprecision in aged mice. |
Engram-specific NPTX2 depletion and overexpression (viral strategies), behavioral fear memory tests, chemogenetic activation of PV+ interneurons as epistasis control |
bioRxivpreprint |
Medium |
bio_10.1101_2025.05.19.654996
|