ArticleJournal of neurochemistry2016
Nicastrin is required for amyloid precursor protein (APP) but not Notch processing, while anterior pharynx-defective 1 is dispensable for processing of both APP and Notch.
Article in Journal of neurochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Plastic associated endocrine disruptors reduce Nicastrin protein and potentiate inflammation in hidradenitis suppurativa skin disease.Nature communications · 2025Article
- Photocleavable Mass-Tagged Oligonucleotide Probes for Multiplexed and Multiomic Tissue Imaging of Targeted Transcripts.Journal of the American Society for Mass Spectrometry · 2025Article
- Probing the Mechanisms of Inhibitors Binding to Presenilin Homologue Using Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2023Article
- Nanoscale organization of Nicastrin, the substrate receptor of the γ-secretase complex, as independent molecular domains.Molecular brain · 2021Article
- Article
- Nicastrin haploinsufficiency alters expression of type I interferon-stimulated genes: the relationship to familial hidradenitis suppurativa.Clinical and experimental dermatology · 2019Article
- Huannao Yicong Formula () regulates γ-secretase activity through APH-1 and PEN-2 gene ragulation pathways in hippocampus of APP/PS1 double transgenic mice.Chinese journal of integrative medicine · 2017Article
- Pen-2 and Presenilin are Sufficient to Catalyze Notch Processing.Journal of Alzheimer's disease : JAD · 2017Article
- Is γ-secretase a beneficial inactivating enzyme of the toxic APP C-terminal fragment C99?The Journal of biological chemistryReview
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The γ-secretase complex is composed of at least four components: presenilin 1 or presenilin-2, nicastrin (NCT), anterior pharynx-defective 1 (Aph-1), and presenilin enhancer 2. In this study, using knockout cell lines, our data demonstrated that knockout of NCT, as well as knockout of presenilin enhancer 2, completely blocked γ-secretase-catalyzed processing of C-terminal fragment (CTF)α and CTFβ, the C-terminal fragments of β-amyloid precursor protein (APP) produced by α-secretase and β-secretase cleavages, respectively. Interestingly, in Aph-1-knockout cells, CTFα and CTFβ were still processed by γ-secretase, indicating Aph-1 is dispensable for APP processing. Furthermore, our results indicate that Aph-1 as well as NCT is not absolutely required for Notch processing, suggesting that NCT is differentially required for APP and Notch processing. In addition, our data revealed that components of the γ-secretase complex are also important for proteasome- and lysosome-dependent degradation of APP and that endogenous APP is mostly degraded by lysosome while exogenous APP is mainly degraded by proteasome. There are unanswered questions regarding the roles of each component of the γ-secretase complex in amyloid precursor protein (APP) and Notch processing. The most relevant, novel finding of this study is that nicastrin (NCT) is required for APP but not Notch processing, while Aph-1 is not essential for processing of both APP and Notch, suggesting NCT as a therapeutic target to restrict Aβ formation without impairing Notch signaling.
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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 Socratic graph.