ArticleInternational journal of Alzheimer's disease2012
Modulation of gamma-secretase for the treatment of Alzheimer's disease.
Article in International journal of Alzheimer's disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed.
- Association of CSF AβNeurology · 2022Trial
- 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
- 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
- Alzheimer's Disease Protein Targets: Comprehensive Review and Future Directions.Current pharmaceutical design · 2025Review
- Identification and Preclinical Evaluation of the Bicyclic Pyrimidine γ-Secretase Modulator BMS-932481.ACS medicinal chemistry letters · 2019Article
- Robust Translation of γ-Secretase Modulator Pharmacology across Preclinical Species and Human Subjects.The Journal of pharmacology and experimental therapeutics · 2016Article
- Natural Product and Natural Product-Derived Gamma Secretase Modulators fromMedicines (Basel, Switzerland) · 2015Review
- Photoaffinity labeling in target- and binding-site identification.Future medicinal chemistry · 2015Review
- A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2015Article
- Abeta, oxidative stress in Alzheimer disease: evidence based on proteomics studies.Biochimica et biophysica acta · 2014Review
- Identification and Preclinical Pharmacology of the γ-Secretase Modulator BMS-869780.International journal of Alzheimer's disease · 2014Article
- Interpreting Alzheimer's disease clinical trials in light of the effects on amyloid-β.Alzheimer's research & therapy · 2014Review
- Efficacy of SPI-1865, a novel gamma-secretase modulator, in multiple rodent models.Alzheimer's research & therapy · 2013Article
- RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors.The Journal of biological chemistryReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Amyloid Hypothesis states that the cascade of events associated with Alzheimer's disease (AD)-formation of amyloid plaques, neurofibrillary tangles, synaptic loss, neurodegeneration, and cognitive decline-are triggered by Aβ peptide dysregulation (Kakuda et al., 2006, Sato et al., 2003, Qi-Takahara et al., 2005). Since γ-secretase is critical for Aβ production, many in the biopharmaceutical community focused on γ-secretase as a target for therapeutic approaches for Alzheimer's disease. However, pharmacological approaches to control γ-secretase activity are challenging because the enzyme has multiple, physiologically critical protein substrates. To lower amyloidogenic Aβ peptides without affecting other γ-secretase substrates, the epsilon (ε) cleavage that is essential for the activity of many substrates must be preserved. Small molecule modulators of γ-secretase activity have been discovered that spare the ε cleavage of APP and other substrates while decreasing the production of Aβ(42). Multiple chemical classes of γ-secretase modulators have been identified which differ in the pattern of Aβ peptides produced. Ideally, modulators will allow the ε cleavage of all substrates while shifting APP cleavage from Aβ(42) and other highly amyloidogenic Aβ peptides to shorter and less neurotoxic forms of the peptides without altering the total Aβ pool. Here, we compare chemically distinct modulators for effects on APP processing and in vivo activity.
Identifiers
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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.