ArticleMolecular neurodegeneration2007
An AICD-based functional screen to identify APP metabolism regulators.
Article in Molecular neurodegeneration, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
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- Genome-Wide CRISPR Screening Identifies Genetic Modulators of Amyloid Precursor Protein Processing.International journal of molecular sciences · 2026Article
- Intracellular protein GBF1 displays significant associations with amyloid pathology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Degradation and inhibition of epigenetic regulatory protein BRD4 exacerbate Alzheimer's disease-related neuropathology in cell models.The Journal of biological chemistry · 2022Article
- Association of the Protein-Quality-Control Protein Ubiquilin-1 With Alzheimer's Disease BothFrontiers in neuroscience · 2022Article
- Mutations in the COPI coatomer subunit α-COP induce release of Aβ-42 and amyloid precursor protein intracellular domain and increase tau oligomerization and release.Neurobiology of aging · 2021Article
- Upregulation of Alzheimer's Disease Amyloid-β Protein Precursor in Astrocytes Both in vitro and in vivo.Journal of Alzheimer's disease : JAD · 2020Article
- Cromolyn Reduces Levels of the Alzheimer's Disease-Associated Amyloid β-Protein by Promoting Microglial Phagocytosis.Scientific reports · 2018Article
- Soluble Gamma-secretase Modulators Attenuate Alzheimer's β-amyloid Pathology and Induce Conformational Changes in Presenilin 1.EBioMedicine · 2017Article
- Nanoplasmonic fiber tip probe detects significant reduction of intracellular Alzheimer's disease-related oligomers by curcumin.Scientific reports · 2017Article
- Mechanisms that synergistically regulate η-secretase processing of APP and Aη-α protein levels: relevance to pathogenesis and treatment of Alzheimer's disease.Discovery medicine · 2017Article
- The Ubiquitin-Proteasome System: Potential Therapeutic Targets for Alzheimer's Disease and Spinal Cord Injury.Frontiers in molecular neuroscience · 2016Review
- Alzheimer's disease-associated mutations increase amyloid precursor protein resistance to γ-secretase cleavage and the Aβ42/Aβ40 ratio.Cell discovery · 2016Article
- Cyclopamine modulates γ-secretase-mediated cleavage of amyloid precursor protein by altering its subcellular trafficking and lysosomal degradation.The Journal of biological chemistry · 2014Article
- Synaptic abnormalities in a Drosophila model of Alzheimer's disease.Disease models & mechanisms · 2014Article
- Article
- Natural Modulators of Amyloid-Beta Precursor Protein Processing.Current Alzheimer research · 2012Article
- Drosophila lilliputian is required for proneural gene expression in retinal development.Developmental dynamics : an official publication of the American Association of Anatomists · 2012Article
- Involvement of ubiquilin-1 transcript variants in protein degradation and accumulation.Communicative & integrative biology · 2011Article
- Alzheimer's disease-associated ubiquilin-1 regulates presenilin-1 accumulation and aggresome formation.Traffic (Copenhagen, Denmark) · 2011Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundA central event in Alzheimer's disease (AD) is the regulated intramembraneous proteolysis of the beta-amyloid precursor protein (APP), to generate the beta-amyloid (Abeta) peptide and the APP intracellular domain (AICD). Abeta is the major component of amyloid plaques and AICD displays transcriptional activation properties. We have taken advantage of AICD transactivation properties to develop a genetic screen to identify regulators of APP metabolism. This screen relies on an APP-Gal4 fusion protein, which upon normal proteolysis, produces AICD-Gal4. Production of AICD-Gal4 induces Gal4-UAS driven luciferase expression. Therefore, when regulators of APP metabolism are modulated, luciferase expression is altered.
resultsTo validate this experimental approach we modulated alpha-, beta-, and gamma-secretase levels and activities. Changes in AICD-Gal4 levels as measured by Western blot analysis were strongly and significantly correlated to the observed changes in AICD-Gal4 mediated luciferase activity. To determine if a known regulator of APP trafficking/maturation and Presenilin1 endoproteolysis could be detected using the AICD-Gal4 mediated luciferase assay, we knocked-down Ubiquilin 1 and observed decreased luciferase activity. We confirmed that Ubiquilin 1 modulated AICD-Gal4 levels by Western blot analysis and also observed that Ubiquilin 1 modulated total APP levels, the ratio of mature to immature APP, as well as PS1 endoproteolysis.
conclusionTaken together, we have shown that this screen can identify known APP metabolism regulators that control proteolysis, intracellular trafficking, maturation and levels of APP and its proteolytic products. We demonstrate for the first time that Ubiquilin 1 regulates APP metabolism in the human neuroblastoma cell line, SH-SY5Y.
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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.