ReviewCold Spring Harbor perspectives in medicine2012
Presenilins and γ-secretase: structure, function, and role in Alzheimer Disease.
Review in Cold Spring Harbor perspectives in medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 250 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
250 citing papers in PubMed, 457 citations in OpenAlex.
- Trial
- The γ-Secretase Modulator, BMS-932481, Modulates Aβ Peptides in the Plasma and Cerebrospinal Fluid of Healthy Volunteers.The Journal of pharmacology and experimental therapeutics · 2016Trial
- AHA1 Regulates Aβ Production via Modulation of APP Abundance and γ-Secretase Assembly.Journal of neurochemistry · 2026Article
- Cerebral Intramural Cells: A Missing Cellular Link Between Vascular Aging and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Interplay between brain-specific microRNAs and Alzheimer's disease.Neural regeneration research · 2026Article
- Dysfunction of the neurovascular unit as a temporal driver in Alzheimer's pathogenesis.Translational neurodegeneration · 2026Review
- Presenilin-dependent regulation of neuronal tau pathology via the autophagy and proteasome pathways.Acta neuropathologica communications · 2026Article
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Modeling Late-Onset Sporadic Alzheimer's Disease Using Patient-Derived Cells: A Review.Neurology international · 2026Review
- Interpretable machine-learning prediction of PSEN1 missense variant pathogenicity based on multi-omics enrichment in six core Alzheimer's disease genes.Alzheimer's research & therapy · 2026Article
- Pharmacology of nivegacetor (RG6289), a potent and selective gamma secretase modulator in clinical development for the treatment of Alzheimer's disease.Frontiers in pharmacology · 2026Article
- From Skin to Brain: Key Genetic Mediators Associating Cutaneous Inflammation and Neurodegenerative Diseases.Genes · 2025Review
- Investigating the binding potential of the Melissa officinalis oil against Alzheimer's targets by molecular docking and in vitro evaluations.Scientific reports · 2025Article
- Mining Alzheimer's Interactomes, Macromolecular Complexes and Pathways for Drug Discovery.Proteomics · 2025Review
- Presenilin Loss Impairs Synaptic Transmission and Causes Axonal Degeneration through Ryanodine Receptor Dysfunction, Independent of γ-Secretase Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Repurposing nirogacestat, a gamma secretase enzyme inhibitor in desmoid tumors.Future oncology (London, England) · 2025Review
- UNC5B is an isoform-dependent target for ectodomain shedding.Journal of biochemistry · 2025Article
- Biologics as Therapeutical Agents Under Perspective Clinical Studies for Alzheimer's Disease.Molecules (Basel, Switzerland) · 2025Review
- Amyloid-β-Induced Neurotoxicity Modulates miR-98 and miR-200 Expression in SH-SY5Y Cells: A Step Toward Alzheimer's Biomarker Discovery.Molecular neurobiology · 2025Article
- An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels.Alzheimer's research & therapy · 2025Article
190 more citing papers are in PubMed but not listed here.
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 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Presenilins were first discovered as sites of missense mutations responsible for early-onset Alzheimer disease (AD). The encoded multipass membrane proteins were subsequently found to be the catalytic components of γ-secretases, membrane-embedded aspartyl protease complexes responsible for generating the carboxyl terminus of the amyloid β-protein (Aβ) from the amyloid protein precursor (APP). The protease complex also cleaves a variety of other type I integral membrane proteins, most notably the Notch receptor, signaling from which is involved in many cell differentiation events. Although γ-secretase is a top target for developing disease-modifying AD therapeutics, interference with Notch signaling should be avoided. Compounds that alter Aβ production by γ-secretase without affecting Notch proteolysis and signaling have been identified and are currently at various stages in the drug development pipeline.
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.