ArticleFrontiers in aging neuroscience2020
γ-Secretase Modulatory Proteins: The Guiding Hand Behind the Running Scissors.
Article in Frontiers in aging neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Pooled it
- Distinct and shared effects of individual γ-secretase inhibitors on human keratinocytes.JID innovations : skin science from molecules to population health · 2026Article
- Neuroinflammation and Secretase Regulation in Alzheimer's Disease: From Molecular Cross-Talk to Multi-Target Therapeutics.International journal of molecular sciences · 2026Review
- From defense to disease: IFITM3 in immunity and Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- The manipulator behind "Scissors": γ -secretase and its modulators in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration.International journal of molecular sciences · 2024Review
- New precision medicine avenues to the prevention of Alzheimer's disease from insights into the structure and function of γ-secretases.The EMBO journal · 2024Review
- Systemic Treatment with siRNA Targeting Gamma-Secretase Activating Protein Inhibits Amyloid-β Accumulation in Alzheimer's Disease.Biomaterials research · 2024Article
- γ-Secretase fanning the fire of innate immunity.Biochemical Society transactions · 2023Review
- The human RAP1 and GFAPɛ proteins increase γ-secretase activity in a yeast model system.G3 (Bethesda, Md.) · 2023Article
- Hypoxia Inducible Factor-1α binds and activates γ-secretase for Aβ production under hypoxia and cerebral hypoperfusion.Molecular psychiatry · 2022Article
- Role of Presenilin-1 in Aggressive Human Melanoma.International journal of molecular sciences · 2022Article
- Modulation of amyloid precursor protein cleavage by γ-secretase activating protein through phase separation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Turning the tide on Alzheimer's disease: modulation of γ-secretase.Cell & bioscience · 2022Review
- Genomics and Functional Genomics of Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer's Disease.Frontiers in neuroscience · 2022Review
- Is γ-secretase a beneficial inactivating enzyme of the toxic APP C-terminal fragment C99?The Journal of biological chemistryReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Described as the "proteasome of the membrane" or the "scissors in the membrane," γ-secretase has notoriously complicated biology, and even after decades of research, the full extent of its regulatory mechanism remains unclear. γ-Secretase is an intramembrane aspartyl protease complex composed of four obligatory subunits: Nicastrin (NCT), Presenilin (PS), Presenilin Enhancer-2 (Pen-2), and Anterior pharynx-defective-1 (Aph-1). γ-Secretase cleaves numerous type 1 transmembrane substrates, with no apparent homology, and plays major roles in broad biological pathways such as development, neurogenesis, and cancer. Notch and the amyloid precursor protein (APP) and are undoubtedly the best-studied γ-secretase substrates because of their role in cancer and Alzheimer's disease (AD) and therefore became the focus of increasing studies as an attractive therapeutic target. The regulation of γ-secretase is intricate and involves the function of multiple cellular entities. Recently, γ-secretase modulatory proteins (GSMPs), which are non-essential subunits and yet modulate γ-secretase activity and specificity, have emerged as an important component in guiding γ-secretase. GSMPs are responsive to cellular and environmental changes and therefore, provide another layer of regulation of γ-secretase. This type of enzymatic regulation allows for a rapid and fine-tuning of γ-secretase activity when appropriate signals appear enabling a temporal level of regulation. In this review article, we discuss the latest developments on GSMPs and implications on the development of effective therapeutics for γ-secretase-associated diseases such as AD and cancer.
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What Socratic 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 Socratic graph.