The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in BACE1 -null mice
Open accessAbstract
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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“Moreover, both mouse lines appear to have reduced levels of anxiety and/or cognitive deficits [18, 56], reduced glutamatergic synapse function and reduced dendritic spine densities [18, 58].”
From Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons (2016) · cites this paper as [58]
In the citing paper
“Indeed, germline and adult conditional BACE1 knockout mice display complex neurological phenotypes.”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [66]
Citations
Cites
Neuregulin 1 and Susceptibility to Schizophrenia
Stefánsson, H., Pétursson, H., Sigurðsson, E., Steinthórsdóttir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/342734 · Cited by 1,671
BACE1 is the major β-secretase for generation of Aβ peptides by neurons
Cai, H., Wang, Y., McCarthy, D. B., Wen, H., Borchelt, D., Price, D. L., & Wong, P. C. (2001) · Nature Neuroscience · doi:10.1038/85064 · Cited by 1,087
Self-citationNeuregulins: functions, forms, and signaling strategies
Falls, D. L. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(02)00102-7 · Cited by 1,071
Axonal Neuregulin-1 Regulates Myelin Sheath Thickness
Michailov, G. V., Sereda, M. W., Brinkmann, B. G., Fischer, T. M., Haug, B., Birchmeier, C., Role, L. W., Lai, C., Schwab, M. H., & Nave, K. (2004) · Science · doi:10.1126/science.1095862 · Cited by 940
Glutamate and Schizophrenia: Beyond the Dopamine Hypothesis
Coyle, J. T. (2006) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-006-9062-8 · Cited by 917
Ross, C. A., Margolis, R. L., Reading, S. A. J., Pletnikov, M. V., & Coyle, J. T. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.015 · Cited by 719
Control of Peripheral Nerve Myelination by the ß-Secretase BACE1
Willem, M., Garratt, A. N., Novak, B., Citron, M., Kaufmann, S., Rittger, A., DeStrooper, B., Saftig, P., Birchmeier, C., & Haass, C. (2006) · Science · doi:10.1126/science.1132341 · Cited by 703
Uranova, N. A., Vostrikov, V. M., Orlovskaya, D. D., & Rachmanova, V. I. (2004) · Schizophrenia Research · doi:10.1016/s0920-9964(03)00181-6 · Cited by 659
Integrative Properties of Radial Oblique Dendrites in Hippocampal CA1 Pyramidal Neurons
Losonczy, A., & Magee, J. C. (2006) · Neuron · doi:10.1016/j.neuron.2006.03.016 · Cited by 641
Bace1 modulates myelination in the central and peripheral nervous system
Hu, X., Hicks, C. W., He, W., Wong, P., Macklin, W. B., Trapp, B. D., & Yan, R. (2006) · Nature Neuroscience · doi:10.1038/nn1797 · Cited by 608
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Amyloid Precursor Protein Processing and Alzheimer's Disease
O'Brien, R. J., & Wong, P. C. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113613 · Cited by 2,061
Self-citationNeuregulin 1 in neural development, synaptic plasticity and schizophrenia
Mei, L., & Xiong, W.-C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2392 · Cited by 1,030
Animal models of schizophrenia
Jones, C., Watson, D., & Fone, K. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01386.x · Cited by 771
The β-Secretase BACE1 in Alzheimer’s Disease
Hampel, H., Vassar, R., De Strooper, B., Hardy, J., Willem, M., Singh, N., Zhou, J., Yan, R., Vanmechelen, E., De Vos, A., et al. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.02.001 · Cited by 694
Targeting the β secretase BACE1 for Alzheimer's disease therapy
Yan, R., & Vassar, R. J. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70276-x · Cited by 645
Metadata
- Authors
- Savonenko, A. V., Melnikova, T., Laird, F. M., Stewart, K.-A., Price, D. L., & Wong, P. C.
- Affiliations
- Johns Hopkins University (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Wong, P. C.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-04-08
- Volume
- 105
- Issue
- 14
- Pages
- 5585-5590
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2291091
- OpenAlex
- W2063978545
- Cited by
- 290
- References
- 39
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 9 · 2020: 6 · 2019: 12 · 2018: 10 · 2017: 16 · 2016: 27 · 2015: 24 · 2014: 23 · 2013: 20 · 2012: 24
- FWCI
- 21.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- Bristol-Myers Squibb Foundation
- Bristol-Myers Squibb
- National Institutes of Health
- National Institute on Aging (P50AG005146, P50AG05146)
- National Institute of Neurological Disorders and Stroke (R01 NS41438, P01NS047308, R01NS041438)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- BACE1, neuregulin-1, ERBB4 signaling, schizophrenia, prepulse inhibition, cognitive impairment, social recognition, clozapine, PSD-95, dendritic spine density, hippocampal pyramidal neurons, synaptic function
- MeSH terms
- Animals, Behavior, Animal, Hippocampus, Schizophrenia, Signal Transduction, Aspartic Acid Endopeptidases, Mice, Knockout, Neuregulin-1, Mice, Amyloid Precursor Protein Secretases, ErbB Receptors, Receptor, ErbB-4
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