ArticleMolecular psychiatry2015
DISC1 regulates trafficking and processing of APP and Aβ generation.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- The impact of Disrupted-in-Schizophrenia 1 (DISC1) on the dopaminergic system: a systematic review.Translational psychiatry · 2017Pooled it
- Levels of aggregation of proteins related to mental illness, assayed by insolubility, vary across the brains of individuals.Scientific reports · 2026Article
- Cytoskeletal control in adult microglia is essential to restore neurodevelopmental synaptic and cognitive deficits.Science advances · 2025Article
- The amyloid precursor protein and its derived fragments concomitantly contribute to the alterations of mitochondrial transport machinery in Alzheimer's disease.Cell death & disease · 2024Article
- Electroacupuncture improves cognitive impairment in diabetic cognitive dysfunction rats by regulating the mitochondrial autophagy pathway.The journal of physiological sciences : JPS · 2022Article
- Regulation of sensorimotor gating via Disc1/Huntingtin-mediated Bdnf transport in the cortico-striatal circuit.Molecular psychiatry · 2022Article
- Induction ofFrontiers in aging neuroscience · 2022Article
- What Can We Learn from Animal Models to Study Schizophrenia?Advances in experimental medicine and biology · 2022Article
- High-sucrose diets contribute to brain angiopathy with impaired glucose uptake and psychosis-related higher brain dysfunctions in mice.Science advances · 2021Article
- 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
- In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia.Biomolecules · 2020Review
- Host-parasite interaction associated with major mental illness.Molecular psychiatry · 2020Article
- Dopamine D1 Receptor (D1R) Expression Is Controlled by a Transcriptional Repressor Complex Containing DISC1.Molecular neurobiology · 2019Article
- The transcriptome landscape associated with Disrupted-in-Schizophrenia-1 locus impairment in early development and adulthood.Schizophrenia research · 2019Article
- Protein misassembly and aggregation as potential convergence points for non-genetic causes of chronic mental illness.Molecular psychiatry · 2019Review
- [Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Disrupted-in-schizophrenia-1 protects synaptic plasticity in a transgenic mouse model of Alzheimer's disease as a mitophagy receptor.Aging cell · 2019Article
- Transgenerational Interaction of Alzheimer's Disease with Schizophrenia through Amyloid Evolvability.Journal of Alzheimer's disease : JAD · 2019Review
- TAR DNA-Binding Protein 43 and Disrupted in Schizophrenia 1 Coaggregation Disrupts Dendritic Local Translation and Mental Function in Frontotemporal Lobar Degeneration.Biological psychiatry · 2018Article
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
We report the novel regulation of proteolytic processing of amyloid precursor protein (APP) by DISC1, a major risk factor for psychiatric illnesses, such as depression and schizophrenia. RNAi knockdown of DISC1 in mature primary cortical neurons led to a significant increase in the levels of intracellular α-C-terminal fragment of APP (APP-CTFα) and the corresponding N-terminal-secreted ectodomain product sAPPα. DISC1 knockdown also elicited a significant decrease in the levels of amyloid beta (Aβ)42 and Aβ40. These aberrant proteolytic events were successfully rescued by co-expression of wild-type DISC1, but not by mutant DISC1 lacking the amino acids required for the interaction with APP, suggesting that APP-DISC1 protein interactions are crucial for the regulation of the C-terminal proteolysis. In a genetically engineered model in which a major full-length DISC1 isoform is depleted, consistent changes in APP processing were seen: an increase in APP-CTFα and decrease in Aβ42 and Aβ40 levels. Finally, we found that knockdown of DISC1 increased the expression of APP at the cell surface and decreased its internalization. The presented DISC1 mechanism of APP proteolytic processing and Aβ peptide generation, which is central to Alzheimer's disease pathology, suggests a novel interface between neurological and psychiatric conditions.
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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.