ReviewCell & bioscience2022
Turning the tide on Alzheimer's disease: modulation of γ-secretase.
Review in Cell & bioscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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
27 citing papers in PubMed, 53 citations in OpenAlex.
- From mechanistic modeling to AI-driven design: computational strategies for targeting the γ-secretase complex.Briefings in bioinformatics · 2026Review
- Levetiracetam prevents Aβ production through SV2a-dependent modulation of APP processing in Alzheimer's disease models.Science translational medicine · 2026Article
- In Silico Phosphoproteomic Analysis Reveals Divergent Regulation of Presenilin 1 and Presenilin 2.Neuromolecular medicine · 2026Article
- Glycogen synthase kinase-3: the master switch driving neurodegeneration in Alzheimer's disease and Parkinson's disease.Archives of toxicology · 2025Review
- Plastic associated endocrine disruptors reduce Nicastrin protein and potentiate inflammation in hidradenitis suppurativa skin disease.Nature communications · 2025Article
- Microglial activation as a hallmark of neuroinflammation in Alzheimer's disease.Metabolic brain disease · 2025Review
- Spectrum of γ-Secretase dysfunction as a unifying predictor of ADAD age at onset across PSEN1, PSEN2 and APP causal genes.Molecular neurodegeneration · 2025Article
- Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review.ACS omega · 2025Review
- The Neuroprotective Effect of Rooibos Herbal Tea Against Alzheimer's Disease: A Review.Molecular nutrition & food research · 2025Review
- The manipulator behind "Scissors": γ -secretase and its modulators in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Molecular Therapeutics in Development to Treat Alzheimer's Disease.Molecular diagnosis & therapy · 2025Review
- Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.Signal transduction and targeted therapy · 2024Review
- Neuroinflammation of Microglial Regulation in Alzheimer's Disease: Therapeutic Approaches.Molecules (Basel, Switzerland) · 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
- APP substrate ectodomain defines amyloid-β peptide length by restraining γ-secretase processivity and facilitating product release.The EMBO journal · 2023Article
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- The human RAP1 and GFAPɛ proteins increase γ-secretase activity in a yeast model system.G3 (Bethesda, Md.) · 2023Article
- Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease.Frontiers in molecular neuroscience · 2023Review
- Multipronged diagnostic and therapeutic strategies for Alzheimer's disease.Chemical science · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is the most common type of neurodegenerative disorder. Amyloid-beta (Aβ) plaques are integral to the "amyloid hypothesis," which states that the accumulation of Aβ peptides triggers a cascade of pathological events leading to neurodegeneration and ultimately AD. While the FDA approved aducanumab, the first Aβ-targeted therapy, multiple safe and effective treatments will be needed to target the complex pathologies of AD. γ-Secretase is an intramembrane aspartyl protease that is critical for the generation of Aβ peptides. Activity and specificity of γ-secretase are regulated by both obligatory subunits and modulatory proteins. Due to its complex structure and function and early clinical failures with pan inhibitors, γ-secretase has been a challenging drug target for AD. γ-secretase modulators, however, have dramatically shifted the approach to targeting γ-secretase. Here we review γ-secretase and small molecule modulators, from the initial characterization of a subset of NSAIDs to the most recent clinical candidates. We also discuss the chemical biology of γ-secretase, in which small molecule probes enabled structural and functional insights into γ-secretase before the emergence of high-resolution structural studies. Finally, we discuss the recent crystal structures of γ-secretase, which have provided valuable perspectives on substrate recognition and molecular mechanisms of small molecules. We conclude that modulation of γ-secretase will be part of a new wave of AD therapeutics.
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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.