ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Insolubility of disrupted-in-schizophrenia 1 disrupts oligomer-dependent interactions with nuclear distribution element 1 and is associated with sporadic mental disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 133 citations in OpenAlex.
- Hubs of long-distance co-alteration characterize brain pathology.Human brain mapping · 2020Pooled it
- Analysis of the DISC1 translocation partner (11q14.3) in genetic risk of schizophrenia.Genes, brain, and behavior · 2012Pooled it
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- Epigenetic Evidence Implies Disturbed Proteostasis and Potentially Protein Aggregation in Suicidality.Biomolecules · 2026Review
- The schizophrenia associated protein DISC1 forms a multivalent tetrameric hub via conserved UVR dimers.Nature communications · 2026Article
- Levels of aggregation of proteins related to mental illness, assayed by insolubility, vary across the brains of individuals.Scientific reports · 2026Article
- Pharmacological rescue of social deficits in rats featuring Disrupted-in-Schizophrenia-1 (DISC1) protein aggregation.Schizophrenia (Heidelberg, Germany) · 2026Article
- Dual phosphorylation of DISC1 at Ser58 and Ser713 regulates polarization of cortical neurons via GSK3β.Science China. Life sciences · 2026Article
- DISC1 Protects Against Zika Virus Infection and Long-Term Neurological Damage Through AMPK-mTOR-Mediated Autophagy.Nature communications · 2025Article
- Social Reward Learning Deficits and Concordant Brain Alterations in Rats Overexpressing Disrupted-in-Schizophrenia 1 (DISC1).The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Protein aggregation identified in olfactory neuronal cells is associated with cognitive impairments in a subset of living schizophrenia patients.Molecular psychiatry · 2025Article
- Tracing the aggregation pathway of the scaffold protein DISC1: Structural implications for chronic mental illnesses.Journal of structural biology: X · 2025Article
- Dysregulation of myelination-related genes in schizophrenia.Journal of neurochemistry · 2024Review
- TransgenicCurrent issues in molecular biology · 2024Article
- SPRTN is involved in hepatocellular carcinoma development through the ER stress response.Cancer gene therapy · 2024Article
- Connectome-based modelling of neurodegenerative diseases: towards precision medicine and mechanistic insight.Nature reviews. Neuroscience · 2023Review
- Article
- Mapping the Domain Structure and Aggregation Propensity of Proteins Using a Gateway Plasmid Vector System.Methods in molecular biology (Clifton, N.J.) · 2023Article
- TRIOBP-1 Protein Aggregation Exists in Both Major Depressive Disorder and Schizophrenia, and Can Occur through Two Distinct Regions of the Protein.International journal of molecular sciences · 2022Article
- Social anhedonia as a Disrupted-in-Schizophrenia 1-dependent phenotype.Scientific reports · 2022Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disrupted-in-schizophrenia 1 (DISC1) and other genes have been identified recently as potential molecular players in chronic psychiatric diseases such as affective disorders and schizophrenia. A molecular mechanism of how these genes may be linked to the majority of sporadic cases of these diseases remains unclear. The chronic nature and irreversibility of clinical symptoms in a subgroup of these diseases prompted us to investigate whether proteins corresponding to candidate genes displayed subtle features of protein aggregation. Here, we show that in postmortem brain samples of a distinct group of patients with phenotypes of affective disorders or schizophrenia, but not healthy controls, significant fractions of DISC1 could be identified as cold Sarkosyl-insoluble protein aggregates. A loss-of-function phenotype could be demonstrated for insoluble DISC1 through abolished binding to a key DISC1 ligand, nuclear distribution element 1 (NDEL1): in human neuroblastoma cells, DISC1 formed expression-dependent, detergent-resistant aggregates that failed to interact with endogenous NDEL1. Recombinant (r) NDEL1 expressed in Escherichia coli selectively bound an octamer of an rDISC1 fragment but not dimers or high molecular weight multimers, suggesting an oligomerization optimum for molecular interactions of DISC1 with NDEL1. For DISC1-related sporadic psychiatric disease, we propose a mechanism whereby impaired cellular control over self-association of DISC1 leads to excessive multimerization and subsequent formation of detergent-resistant aggregates, culminating in loss of ligand binding, here exemplified by NDEL1. We conclude that the absence of oligomer-dependent ligand interactions of DISC1 can be associated with sporadic mental disease of mixed phenotypes.
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