ArticleProceedings of the National Academy of Sciences of the United States of America2008
Deficiency of Aph1B/C-gamma-secretase disturbs Nrg1 cleavage and sensorimotor gating that can be reversed with antipsychotic treatment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 84 citations in OpenAlex.
- Trial
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- γ-Secretase-Mediated Endoproteolysis of Neuregulin-1 and E-Cadherin.Biochemistry · 2025Article
- Neuregulin1 Nuclear Signaling Influences Adult Neurogenesis and Regulates a Schizophrenia Susceptibility Gene Network within the Mouse Dentate Gyrus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Nrg1 intracellular signaling regulates the development of interhemispheric callosal axons in mice.Life science alliance · 2024Article
- Selective inhibitors of the PSEN1-gamma-secretase complex.The Journal of biological chemistry · 2023Article
- Role of the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in the anti-psychotic effects of aripiprazole and sertindole in ketamine-induced schizophrenia-like behaviors in rats.Inflammopharmacology · 2022Article
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- The Complex Work of Proteases and Secretases in Wallerian Degeneration: Beyond Neuregulin-1.Frontiers in cellular neuroscience · 2019Review
- Nrg1 Intracellular Signaling Is Neuroprotective upon Stroke.Oxidative medicine and cellular longevity · 2019Article
- Antibody-mediated stabilization of NRG1 induces behavioral and electrophysiological alterations in adult mice.Scientific reports · 2018Article
- Neuregulin 3 and its roles in schizophrenia risk and presentation.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2018Review
- Inactivation of γ-secretases leads to accumulation of substrates and non-Alzheimer neurodegeneration.EMBO molecular medicine · 2017Article
- Regulation of striatal dopamine responsiveness by Notch/RBP-J signaling.Translational psychiatry · 2017Article
- Sub-chronic Antipsychotic Drug Administration Reverses the Expression of Neuregulin 1 and ErbB4 in a Cultured MK801-Induced Mouse Primary Hippocampal Neuron or a Neurodevelopmental Schizophrenia Model.Neurochemical research · 2016Article
- Loss of Nicastrin from Oligodendrocytes Results in Hypomyelination and Schizophrenia with Compulsive Behavior.The Journal of biological chemistry · 2016Article
- Article
- Proteolytic Processing of Neuregulin 1 Type III by Three Intramembrane-cleaving Proteases.The Journal of biological chemistry · 2016Article
- Calcyon stimulates neuregulin 1 maturation and signaling.Molecular psychiatry · 2015Article
- Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulated intramembrane proteolysis by gamma-secretase cleaves proteins in their transmembrane domain and is involved in important signaling pathways. At least four different gamma-secretase complexes have been identified, but little is known about their biological role and specificity. Previous work has demonstrated the involvement of the Aph1A-gamma-secretase complex in Notch signaling, but no specific function could be assigned to Aph1B/C-gamma-secretase. We demonstrate here that the Aph1B/C-gamma-secretase complex is expressed in brain areas relevant to schizophrenia pathogenesis and that Aph1B/C deficiency causes pharmacological and behavioral abnormalities that can be reversed by antipsychotic drugs. At the molecular level we find accumulation of Nrg1 fragments in the brain of Aph1BC(-/-) mice. Our observations gain clinical relevance by the demonstration that a Val-to-Leu mutation in the Nrg1 transmembrane domain, associated with increased risk for schizophrenia, affects gamma-secretase cleavage of Nrg1. This finding suggests that dysregulation of intramembrane proteolysis of Nrg1 could increase risk for schizophrenia and related disorders.
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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.