ArticleScientific reports2015
The FDA-approved natural product dihydroergocristine reduces the production of the Alzheimer's disease amyloid-β peptides.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
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- Combined targeting of glioblastoma stem cells of different cellular states disrupts malignant progression.Nature communications · 2025Article
- Dihydroergotamine and Bromocriptine: Potential Drugs for the Treatment of Major Depressive Disorder and Alzheimer's Disease Comorbidity.Molecular neurobiology · 2025Article
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- Targeting Amyloidogenic Processing of APP in Alzheimer's Disease.Frontiers in molecular neuroscience · 2020Review
- The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway.Oxidative medicine and cellular longevity · 2019Review
- Ergot Alkaloid Synthesis Capacity of Penicillium camemberti.Applied and environmental microbiology · 2018Article
- Amyloid beta modulators and neuroprotection in Alzheimer's disease: a critical appraisal.Drug discovery today · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Known γ-secretase inhibitors or modulators display an undesirable pharmacokinetic profile and toxicity and have therefore not been successful in clinical trials for Alzheimer's disease (AD). So far, no compounds from natural products have been identified as direct inhibitors of γ-secretase. To search for bioactive molecules that can reduce the amount of amyloid-beta peptides (Aβ) and that have better pharmacokinetics and an improved safety profile, we completed a screen of ~400 natural products by using cell-based and cell-free γ-secretase activity assays. We identified dihydroergocristine (DHEC), a component of an FDA- (Food and Drug Administration)-approved drug, to be a direct inhibitor of γ-secretase. Micromolar concentrations of DHEC substantially reduced Aβ levels in different cell types, including a cell line derived from an AD patient. Structure-activity relationship studies implied that the key moiety for inhibiting γ-secretase is the cyclized tripeptide moiety of DHEC. A Surface Plasmon Resonance assay showed that DHEC binds directly to γ-secretase and Nicastrin, with equilibrium dissociation constants (Kd) of 25.7 nM and 9.8 μM, respectively. This study offers DHEC not only as a new chemical moiety for selectively modulating the activity of γ-secretase but also a candidate for drug repositioning in Alzheimer's disease.
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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.