ReviewNeuroscience letters2019
γ-Secretase and its modulators: Twenty years and beyond.
Review in Neuroscience letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Genome-wide association analyses identify candidate loci for amyloid imaging and plasma biomarkers in adults with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Drug delivery strategies with lipid-based nanoparticles for Alzheimer's disease treatment.Journal of nanobiotechnology · 2025Review
- Comprehending Alzheimer's Disease: Molecular Mechanisms and Treatment Strategies.Current Alzheimer research · 2025Review
- Rotenone Induces a Neuropathological Phenotype in Cholinergic-like Neurons Resembling Parkinson's Disease Dementia (PDD).Neurotoxicity research · 2024Article
- Computational Studies to Understand the Neuroprotective Mechanism of Action Basil Compounds.Molecules (Basel, Switzerland) · 2023Article
- The functional role of Higd1a in mitochondrial homeostasis and in multiple disease processes.Genes & diseases · 2023Review
- Notch pathway is required for protection against heat stress in spermatogonial stem cells in medaka.Fish physiology and biochemistry · 2023Article
- CDiP technology for reverse engineering of sporadic Alzheimer's disease.Journal of human genetics · 2023Review
- The Amyloid Cascade Hypothesis in Alzheimer's Disease: Should We Change Our Thinking?Biomolecules · 2023Review
- Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease.Frontiers in molecular neuroscience · 2023Review
- The role of amyloid β in the pathological mechanism of GNE myopathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Review
- Notch signaling in malignant gliomas: supporting tumor growth and the vascular environment.Cancer metastasis reviews · 2022Review
- CD44 In Sarcomas: A Comprehensive Review and Future Perspectives.Frontiers in oncology · 2022Review
- Genomics and Functional Genomics of Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Synthesis and Characterization of Andrographolide Derivatives as Regulators of βAPP Processing in Human Cells.Molecules (Basel, Switzerland) · 2021Article
- The Potential of Gamma Secretase as a Therapeutic Target for Cardiac Diseases.Journal of personalized medicine · 2021Review
- Notch signaling via Hey1 and Id2b regulates Müller glia's regenerative response to retinal injury.Glia · 2021Article
- Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue.Molecules (Basel, Switzerland) · 2021Article
- Bridging Scales in Alzheimer's Disease: Biological Framework for Brain Simulation With The Virtual Brain.Frontiers in neuroinformatics · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Twenty years ago, Wolfe, Xia, and Selkoe identified two aspartate residues in Alzheimer's presenilin protein that constitute the active site of the γ-secretase complex. Mutations in the genes encoding amyloid precursor protein (APP) or presenilin (PS) cause early onset familial Alzheimer's disease (AD), and sequential cleavages of the APP by β-secretase and γ-secretase/presenilin generate amyloid β protein (Aβ), the major component of pathological hallmark, neuritic plaques, in brains of AD patients. Therapeutic strategies centered on targeting γ-secretase/presenilin to reduce amyloid were implemented and led to several high profile clinical trials. This review article focuses on the studies of γ-secretase and its inhibitors/modulators since the discovery of presenilin as the γ-secretase. While a lack of complete understanding of presenilin biology renders failure of clinical trials, the lessons learned from some γ-secretase modulators, while premature for human testing, provide new directions to develop potential therapeutics. Imbalanced Aβ homeostasis is an upstream event of neurodegenerative processes. Exploration of γ-secretase modulators for their roles in these processes is highly significant, e.g., decreasing neuroinflammation and levels of phosphorylated tau, the component of the other AD pathological hallmark, neurofibrillary tangles. Agents with excellent human pharmacology hold great promise in suppressing neurodegeneration in pre-symptomatic or early stage AD patients.
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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.