ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Disrupted-in-Schizophrenia-1 Attenuates Amyloid-β Generation and Cognitive Deficits in APP/PS1 Transgenic Mice by Reduction of β-Site APP-Cleaving Enzyme 1 Levels.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 23 citations in OpenAlex.
- Distinct Transcriptional States of TDP-43 Pathology in an Alzheimer's Disease Mouse Model.Neuroscience bulletin · 2026Article
- Levels of aggregation of proteins related to mental illness, assayed by insolubility, vary across the brains of individuals.Scientific reports · 2026Article
- Endothelial delivery of simvastatin by LRP1-targeted nanoparticles ameliorates pathogenesis of alzheimer's disease in a mouse model.Alzheimer's research & therapy · 2025Article
- Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- HDAC9-mediated calmodulin deacetylation induces memory impairment in Alzheimer's disease.CNS neuroscience & therapeutics · 2024Article
- Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.Current neuropharmacology · 2023Article
- Reducing Nav1.6 expression attenuates the pathogenesis of Alzheimer's disease by suppressing BACE1 transcription.Aging cell · 2022Article
- Effects of DISC1 on Alzheimer's disease cell models assessed by iTRAQ proteomics analysis.Bioscience reports · 2022Article
- The plasma peptides of Alzheimer's disease.Clinical proteomics · 2021Article
- Functional brain defects in a mouse model of a chromosomal t(1;11) translocation that disrupts DISC1 and confers increased risk of psychiatric illness.Translational psychiatry · 2021Article
- Protein misassembly and aggregation as potential convergence points for non-genetic causes of chronic mental illness.Molecular psychiatry · 2019Review
- Disrupted-in-schizophrenia-1 protects synaptic plasticity in a transgenic mouse model of Alzheimer's disease as a mitophagy receptor.Aging cell · 2019Article
- Mitochondrial Dysfunction in Neural Injury.Frontiers in neuroscience · 2019Review
- The Mitochondrion: A Potential Therapeutic Target for Alzheimer's Disease.Neuroscience bulletin · 2018Review
- Bis(9)-(-)-Meptazinol, a novel dual-binding AChE inhibitor, rescues cognitive deficits and pathological changes in APP/PS1 transgenic mice.Translational neurodegeneration · 2018Article
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12 authors at 4 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Disrupted-in-Schizophrenia-1 (DISC1) is a genetic risk factor for a wide range of major mental disorders, including schizophrenia, major depression, and bipolar disorders. Recent reports suggest a potential role of DISC1 in the pathogenesis of Alzheimer's disease (AD), by referring to an interaction between DISC1 and amyloid precursor protein (APP), and to an association of a single-nucleotide polymorphism in a DISC1 intron and late onset of AD. However, the function of DISC1 in AD remains unknown. In this study, decreased levels of DISC1 were observed in the cortex and hippocampus of 8-month-old APP/PS1 transgenic mice, an animal model of AD. Overexpression of DISC1 reduced, whereas knockdown of DISC1 increased protein levels, but not mRNA levels of β-site APP-Cleaving Enzyme 1 (BACE1), a key enzyme in amyloid-β (Aβ) generation. Reduction of BACE1 protein levels by overexpression of DISC1 was accompanied by an accelerating decline rate of BACE1, and was blocked by the lysosomal inhibitor chloroquine, rather than proteasome inhibitor MG-132. Moreover, overexpression of DISC1 in the hippocampus with an adeno-associated virus reduced the levels of BACE1, soluble Aβ40/42, amyloid plaque density, and rescued cognitive deficits of APP/PS1 transgenic mice. These results indicate that DISC1 attenuates Aβ generation and cognitive deficits of APP/PS1 transgenic mice through promoting lysosomal degradation of BACE1. Our findings provide new insights into the role of DISC1 in AD pathogenesis and link a potential function of DISC1 to the psychiatric symptoms of AD.
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