ReviewThe EMBO journal2024
New precision medicine avenues to the prevention of Alzheimer's disease from insights into the structure and function of γ-secretases.
Review in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Medicinal seahorses (Hippocampus spp.) for Alzheimer's disease within species conservation framework: an integrated review of ethnopharmacology, bioactivity, bibliometrics, and network pharmacology.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- A new era in neuropharmacology: assessing the efficacy and safety of novel anti-amyloid and non-amyloid drug targets for Alzheimer's disease.Journal of neurology · 2026Review
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Hepatic HMGCS2-derived β-hydroxybutyrate attenuates hippocampal insulin resistance and neuroinflammation to promote MASLD-induced cognitive function.Communications biology · 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
- CTAD taskforce: genetic therapies in Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
- A manifesto for Alzheimer's disease drug discovery in the era of disease-modifying therapies.Molecular neurodegeneration · 2025Review
- Maintaining the Integral Membrane Proteome: Revisiting the Functional Repertoire of Integral Membrane Proteases.Chembiochem : a European journal of chemical biology · 2025Review
- ELK1 inhibition alleviates amyloid pathology and memory decline by promoting the SYVN1-mediated ubiquitination and degradation of PS1 in Alzheimer's disease.Experimental & molecular medicine · 2025Article
- Spectrum of γ-Secretase dysfunction as a unifying predictor of ADAD age at onset across PSEN1, PSEN2 and APP causal genes.Molecular neurodegeneration · 2025Article
- Peripheral proteinopathy in neurodegenerative diseases.Translational neurodegeneration · 2025Review
- The manipulator behind "Scissors": γ -secretase and its modulators in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Biomarkers and therapeutic targets in early Alzheimer's disease: an Olink proteomics study.Frontiers in neurology · 2025Article
- Molecular Therapeutics in Development to Treat Alzheimer's Disease.Molecular diagnosis & therapy · 2025Review
- The curious case of a heterozygous loss-of-functionMolecular neurodegeneration advances · 2025Article
- Homeostatic microglia initially seed and activated microglia later reshape amyloid plaques in Alzheimer's Disease.Nature communications · 2024Article
- Pathophysiologic abnormalities in transgenic mice carrying the Alzheimer disease PSEN1 Δ440 mutation.Human molecular genetics · 2024Article
- Pathologic subtyping of Alzheimer's disease brain tissue reveals disease heterogeneity.medRxiv : the preprint server for health sciences · 2024Article
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 2 institutions in 3 countries.
Funding
Abstract
Two phase-III clinical trials with anti-amyloid peptide antibodies have met their primary goal, i.e. slowing of Alzheimer's disease (AD) progression. However, antibody therapy may not be the optimal therapeutic modality for AD prevention, as we will discuss in the context of the earlier small molecules described as "γ-secretase modulators" (GSM). We review here the structure, function, and pathobiology of γ-secretases, with a focus on how mutations in presenilin genes result in early-onset AD. Significant progress has been made in generating compounds that act in a manner opposite to pathogenic presenilin mutations: they stabilize the proteinase-substrate complex, thereby increasing the processivity of substrate cleavage and altering the size spectrum of Aβ peptides produced. We propose the term "γ-secretase allosteric stabilizers" (GSAS) to distinguish these compounds from the rather heterogenous class of GSM. The GSAS represent, in theory, a precision medicine approach to the prevention of amyloid deposition, as they specifically target a discrete aspect in a complex cell biological signalling mechanism that initiates the pathological processes leading to Alzheimer's disease.
Indexed as
Identifiers
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.