ArticleScience advances2021
A biomarker-authenticated model of schizophrenia implicating NPTX2 loss of function.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Loss of schizophrenia risk gene XPO7 disrupts neuronal excitability and network regularity via altered NaMolecular psychiatry · 2026Article
- Genomic dimensions deconstruct the clinical heterogeneity of bipolar disorder.Research square · 2026Article
- Schizophrenia Spectrum Biomarkers Consortium: Establishment of a Biorepository for the Discovery of Quantitative Fluid Biomarkers.Schizophrenia bulletin · 2026Article
- Cerebrospinal fluid biomarkers reveal transdiagnostic synaptic dysfunction across major psychiatric disorders.Nature communications · 2026Article
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- Article
- Association between neuronal pentraxin 2, ADHD symptoms, and executive functioning in adults with ADHD: a case-control study.European archives of psychiatry and clinical neuroscience · 2026Article
- Mapping spatially organized molecular and genetic signatures of schizophrenia across multiple scales in human prefrontal cortex.bioRxiv : the preprint server for biology · 2026Article
- CSF Levels of NPTX2 Are Associated With Less Brain Atrophy Over Time in Cognitively Unimpaired Individuals.Annals of clinical and translational neurology · 2026Article
- Tuning excitatory input to fast-spiking parvalbumin-positive interneurons: a lever for plasticity and hyperexcitability across the lifespan.Frontiers in synaptic neuroscience · 2026Article
- Associations of cerebrospinal fluid measures of synaptic function with white matter microstructure and cognition in older adults.Frontiers in aging neuroscience · 2026Article
- Mass Spectrometry-Based Quantification of Orexin Species in Human Cerebrospinal Fluid Reveals Differential Dynamics Associated with Sleep.medRxiv : the preprint server for health sciences · 2025Article
- SLEEP AND NEURODEGENERATION: EXAMINING POTENTIAL PHYSIOLOGICAL MECHANISMS.Current sleep medicine reports · 2025Article
- Cognitive resilience in preclinical Alzheimer's disease: Higher NPTX2 and VGF levels are associated with reduced cognitive decline.Neurobiology of aging · 2025Article
- Transcriptomic and protein analysis of human cortex reveals genes and pathways linked to NPTX2 disruption in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Altered NPTX2 dynamics associated with impaired cognitive aging.bioRxiv : the preprint server for biology · 2025Article
- Disturbed engram network caused by NPTX downregulation underlies aging-related contextual fear memory deficits.Cell research · 2025Article
- 3-Phenoxybenzoic Acid Induces Neuronal Pentraxin 2 to Upregulate Complement Activity and Promotes Microglia-Mediated Neuronal Synaptic Damage.Journal of molecular neuroscience : MN · 2025Article
- In-Depth Cell-Type-Specific Proteome Landscape of the Brain from Human Amyloid-β Overexpression Mouse Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Levels of neuronal pentraxin 2 in plasma is associated with cognitive function in patients with schizophrenia.Psychopharmacology · 2024Article
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset schizophrenia. NPTX2 plays an essential role in maintaining excitatory homeostasis by adaptively enhancing circuit inhibition. NPTX2 function requires activity-dependent exocytosis and dynamic shedding at synapses and is coupled to circadian behavior. Behavior-linked NPTX2 trafficking is abolished by mutations that disrupt select activity-dependent plasticity mechanisms of excitatory neurons. Modeling NPTX2 loss of function results in failure of parvalbumin interneurons in their adaptive contribution to behavioral stress, and animals exhibit multiple neuropsychiatric domains. Because the genetics of schizophrenia encompasses diverse proteins that contribute to excitatory synapse plasticity, the identified vulnerability of NPTX2 function can provide a framework for assessing the impact of genetics and the intersection with stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.