ArticleProceedings of the National Academy of Sciences of the United States of America2004
Processing of Notch and amyloid precursor protein by gamma-secretase is spatially distinct.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 108 citations in OpenAlex.
- Article
- The manipulator behind "Scissors": γ -secretase and its modulators in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Construction of a Dataset for All Expressed Transcripts for Alzheimer's Disease Research.Brain sciences · 2024Article
- Notch signaling functions in noncanonical juxtacrine manner in platelets to amplify thrombogenicity.eLife · 2022Article
- γ-Secretase Modulatory Proteins: The Guiding Hand Behind the Running Scissors.Frontiers in aging neuroscience · 2020Article
- New treatment modalities in Alzheimer's disease.World journal of clinical cases · 2019Review
- Prevention of excitotoxicity-induced processing of BDNF receptor TrkB-FL leads to stroke neuroprotection.EMBO molecular medicine · 2019Article
- Alzheimer Aβ Assemblies Accumulate in Excitatory Neurons upon Proteasome Inhibition and Kill Nearby NAKα3 Neurons by Secretion.iScience · 2019Article
- Peptides as Potential Therapeutics for Alzheimer's Disease.Molecules (Basel, Switzerland) · 2018Review
- Alzheimer's disease hypothesis and related therapies.Translational neurodegeneration · 2018Review
- Structural and Chemical Biology of Presenilin Complexes.Cold Spring Harbor perspectives in medicine · 2017Review
- Loss of presenilin 2 is associated with increased iPLA2 activity and lung tumor development.Oncogene · 2014Article
- The Amyloid Precursor Protein is rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid.Molecular brain · 2014Article
- Membrane tethered delta activates notch and reveals a role for spatio-mechanical regulation of the signaling pathway.Biophysical journal · 2013Article
- γ-Secretase inhibitors and modulators.Biochimica et biophysica acta · 2013Review
- Structural biology of presenilins and signal peptide peptidases.The Journal of biological chemistry · 2013Review
- Modeling Alzheimer's disease in mouse without mutant protein overexpression: cooperative and independent effects of Aβ and tau.PloS one · 2013Article
- Retention in endoplasmic reticulum 1 (RER1) modulates amyloid-β (Aβ) production by altering trafficking of γ-secretase and amyloid precursor protein (APP).The Journal of biological chemistry · 2012Article
- The role of endocytosis in activating and regulating signal transduction.Cellular and molecular life sciences : CMLS · 2012Review
- Trafficking and proteolytic processing of APP.Cold Spring Harbor perspectives in medicine · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
gamma-Secretase activity is associated with a presenilin (PS)-containing macromolecular complex. Whether PS contains the active site of gamma-secretase has been controversial. One challenge is to find PS that is engaged in the active gamma-secretase complex at the cell surface, where some substrates appear to be processed. In this study, we developed an intact cell photolabeling technique that allows the direct visualization of active gamma-secretase at the cell surface. We demonstrated that active gamma-secretase is present in the plasma membrane. Moreover, the PS1 heterodimer is specifically photolabeled at the cell surface by a potent inhibitor that binds to only the active gamma-secretase. We also explored the cellular processing sites of gamma-secretase for amyloid precursor protein (APP) and Notch by using small molecular probes. MRL631, a gamma-secretase inhibitor that is unable to penetrate the cell membrane, significantly blocks gamma-secretase-mediated Notch cleavage but has little effect on APP processing. These results indicate that Notch is processed at the cell surface and that the majority of APP is processed by intracellular gamma-secretase. Furthermore, the fact that inhibitors first target gamma-secretase in the plasma membrane for Notch processing, and not for APP, will have important implications for drug development to treat Alzheimer's disease and cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.