ArticleProceedings of the National Academy of Sciences of the United States of America2008
Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in BACE1-null mice.
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 161 papers.
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Who cites it
161 citing papers in PubMed, 282 citations in OpenAlex.
- Trial
- Achieving protease substrate-specific inhibition by mAb dual functional selections.Protein science : a publication of the Protein Society · 2026Article
- Age-dependent biphasic alterations and protein-activity decoupling of plasma BACE1 in major depressive disorder.Frontiers in psychiatry · 2026Article
- Exploration of schizophrenia-related behavioral and molecular abnormalities in a mutant mouse model with a mutation in the TVV motif of the ErbB4 gene.Molecular brain · 2025Article
- Proposed Therapeutic Strategy to Combat Alzheimer's Disease by Targeting Beta and Gamma Secretases.Current Alzheimer research · 2025Review
- Rethinking antisense oligonucleotide therapeutics for amyotrophic lateral sclerosis.Annals of clinical and translational neurology · 2024Review
- Exploring the Frontier: Antisense Long Non-Coding RNAs as Key Regulators in Alzheimer's Disease.Aging and disease · 2024Review
- ADME profiling, molecular docking, DFT, and MEP analysis reveal cissamaline, cissamanine, and cissamdine fromRSC advances · 2024Article
- Amyloid-β in Alzheimer's disease: Structure, toxicity, distribution, treatment, and prospects.Ibrain · 2024Review
- BACE1 in PV interneuron tunes hippocampal CA1 local circuits and resets priming of fear memory extinction.Molecular psychiatry · 2023Article
- Importance of Control Groups for Evaluating Long-Term Behavioral and Cognitive Outcomes of Controlled Cortical Impact in Immature Rats.Journal of neurotrauma · 2023Article
- Review
- Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.Current neuropharmacology · 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
- Finding New Ways How to Control BACE1.The Journal of membrane biology · 2022Article
- Lipid flippase dysfunction as a therapeutic target for endosomal anomalies in Alzheimer's disease.iScience · 2022Article
- Induction ofFrontiers in aging neuroscience · 2022Article
- Homer1a regulates Shank3 expression and underlies behavioral vulnerability to stress in a model of Phelan-McDermid syndrome.Cell reports · 2021Article
- BACE1 controls synaptic function through modulating release of synaptic vesicles.Molecular psychiatry · 2021Article
- Mental Illness and Amyloid: A Scoping Review of Scientific Evidence over the Last 10 Years (2011 to 2021).Brain sciences · 2021Article
101 more citing papers are in PubMed but not listed here.
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6 authors at 4 institutions in 1 country.
Funding
Abstract
beta-Site APP-cleaving enzyme 1 (BACE1) is required for the penultimate cleavage of the amyloid-beta precursor protein (APP) leading to the generation of amyloid-beta peptides that is central to the pathogenesis of Alzheimer's disease. In addition to its role in endoproteolysis of APP, BACE1 participates in the proteolytic processing of neuregulin 1 (NRG1) and influences the myelination of central and peripheral axons. Although NRG1 has been genetically linked to schizophrenia and NRG1(+/-) mice exhibit a number of schizophrenia-like behavioral traits, it is not known whether altered BACE1-dependent NRG1 signaling can cause similar behavioral abnormalities. To test this hypothesis, we analyze the behaviors considered to be rodent analogs of clinical features of schizophrenia in BACE1(-/-) mice with impaired processing of NRG1. We demonstrate that BACE1(-/-) mice exhibit deficits in prepulse inhibition, novelty-induced hyperactivity, hypersensitivity to a glutamatergic psychostimulant (MK-801), cognitive impairments, and deficits in social recognition. Importantly, some of these manifestations were responsive to treatment with clozapine, an atypical antipsychotic drug. Moreover, although the total amount of ErbB4, a receptor for NRG1 was not changed, binding of ErbB4 with postsynaptic density protein 95 (PSD95) was significantly reduced in the brains of BACE1(-/-) mice. Consistent with the role of ErbB4 in spine morphology and synaptic function, BACE1(-/-) mice displayed reduced spine density in hippocampal pyramidal neurons. Collectively, our findings suggest that alterations in BACE1-dependent NRG1/ErbB4 signaling may participate in the pathogenesis of schizophrenia and related psychiatric disorders.
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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.