ReviewCell stress2018
Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase.
Review in Cell stress, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Probiotics for Alzheimer's Disease: A Systematic Review.Nutrients · 2021Pooled it
- Association of CSF AβNeurology · 2022Trial
- Amino Acid-Driven Gold Nanochaperone Platforms for Alzheimer's Therapy: A Mechanistic and Design Framework for Protein Misfolding Modulation.Molecular neurobiology · 2026Review
- Transport pathways across the blood-brain barrier for waste clearance and drug delivery.Fluids and barriers of the CNS · 2026Review
- Sovateltide at the heart-brain axis crosstalk in Alzheimer's disease: a promising multi-target and cutting-edge therapeutic approach.Inflammopharmacology · 2026Review
- Conformational Flexibility of Transmembrane Helices: How it Works and Where it Matters.Chemical reviews · 2026Review
- Recapitulating Alzheimer's disease pathophysiology with a microfluidic neurospheroid-grafted endothelial barrier model.Molecular brain · 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
- Analysis of Specific Serum Markers for Early Prediction of Alzheimer's Disease in Adolescents with Down Syndrome.Indian journal of clinical biochemistry : IJCB · 2025Article
- Charting γ-secretase substrates by explainable AI.Nature communications · 2025Article
- Growth associated protein 43 (GAP-43) predicts brain amyloidosis in Alzheimer's dementia continuum: an [BMC neurology · 2025Article
- Morphological and Molecular Profiling of Amyloid-β Species in Alzheimer's Pathogenesis.Molecular neurobiology · 2025Review
- EBP1 potentiates amyloid β pathology by regulating γ-secretase.Nature aging · 2025Article
- γ-Secretase modulator resistance of an aggressive Alzheimer-causing presenilin mutant can be overcome in the heterozygous patient state by a set of advanced compounds.Alzheimer's research & therapy · 2025Article
- Pathophysiologic abnormalities in transgenic mice carrying the Alzheimer disease PSEN1 Δ440 mutation.Human molecular genetics · 2024Article
- Cryo-EM structures of cotton wool plaques' amyloid β and of tau filaments in dominantly inherited Alzheimer disease.Acta neuropathologica · 2024Article
- Cryo-EM structures of amyloid-β and tau filaments in Down syndrome.Nature structural & molecular biology · 2024Article
- Conformational Changes and Unfolding of β-Amyloid Substrates in the Active Site of γ-Secretase.International journal of molecular sciences · 2024Article
- Neuropathological and sociodemographic factors associated with the cortical amyloid load in aging and Alzheimer's disease.GeroScience · 2024Article
- Exploring the AβFrontiers in molecular biosciences · 2024Article
2 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
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer´s disease (AD) is a devastating neurodegenerative disease of the elderly population. Genetic evidence strongly suggests that aberrant generation and/or clearance of the neurotoxic amyloid-β peptide (Aβ) is triggering the disease. Aβ is generated from the amyloid precursor protein (APP) by the sequential cleavages of β- and γ-secretase. The latter cleavage by γ-secretase, a unique and fascinating four-component protease complex, occurs in the APP transmembrane domain thereby releasing Aβ species of 37-43 amino acids in length including the longer, highly pathogenic peptides Aβ42 and Aβ43. The lack of a precise understanding of Aβ generation as well as of the functions of other γ-secretase substrates has been one factor underlying the disappointing failure of γ-secretase inhibitors in clinical trials, but on the other side also been a major driving force for structural and in depth mechanistic studies on this key AD drug target in the past few years. Here we review recent breakthroughs in our understanding of how the γ-secretase complex recognizes substrates, of how it binds and processes β-secretase cleaved APP into different Aβ species, as well as the progress made on a question of outstanding interest, namely how clinical AD mutations in the catalytic subunit presenilin and the γ-secretase cleavage region of APP lead to relative increases of Aβ42/43. Finally, we discuss how the knowledge emerging from these studies could be used to therapeutically target this enzyme in a safe way.
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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 OpenQuestion graph.