ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Steroids as γ-secretase modulators.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Biological Sex Disparities in Alzheimer's Disease.Current topics in behavioral neurosciences · 2025Review
- Gut-Brain Axis: Focus on Sex Differences in Neuroinflammation.International journal of molecular sciences · 2024Review
- A multi-omics investigation of the composition and function of extracellular vesicles along the temporal trajectory of COVID-19.Nature metabolism · 2021Article
- Embedded in the Membrane: How Lipids Confer Activity and Specificity to Intramembrane Proteases.The Journal of membrane biology · 2018Article
- An exploratory investigation of brain-selective estrogen treatment in males using a mouse model of Alzheimer's disease.Hormones and behavior · 2018Article
- Short Aβ peptides attenuate Aβ42 toxicity in vivo.The Journal of experimental medicine · 2018Article
- Induction of Amyloid-β42 Production by Fipronil and Other Pyrazole Insecticides.Journal of Alzheimer's disease : JAD · 2018Article
- Middle-Aged Diabetic Females and Males Present Distinct Susceptibility to Alzheimer Disease-like Pathology.Molecular neurobiology · 2017Article
- Identification of "sarsasapogenin-aglyconed" timosaponins as novel Aβ-lowering modulators of amyloid precursor protein processing.Chemical science · 2016Article
- Ovarian hormones ameliorate memory impairment, cholinergic deficit, neuronal apoptosis and astrogliosis in a rat model of Alzheimer's disease.Experimental and therapeutic medicine · 2016Article
- Cholestenoic acid, an endogenous cholesterol metabolite, is a potent γ-secretase modulator.Molecular neurodegeneration · 2015Article
- Article
- Sex differences in cognitive impairment and Alzheimer's disease.Frontiers in neuroendocrinology · 2014Review
- Complex relationships between substrate sequence and sensitivity to alterations in γ-secretase processivity induced by γ-secretase modulators.Biochemistry · 2014Article
- γ-Secretase processing and effects of γ-secretase inhibitors and modulators on long Aβ peptides in cells.The Journal of biological chemistry · 2014Article
- Cross-talk of membrane lipids and Alzheimer-related proteins.Molecular neurodegeneration · 2013Review
- Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Aggregation and accumulation of Aβ42 play an initiating role in Alzheimer's disease (AD); thus, selective lowering of Aβ42 by γ-secretase modulators (GSMs) remains a promising approach to AD therapy. Based on evidence suggesting that steroids may influence Aβ production, we screened 170 steroids at 10 μM for effects on Aβ42 secreted from human APP-overexpressing Chinese hamster ovary cells. Many acidic steroids lowered Aβ42, whereas many nonacidic steroids actually raised Aβ42. Studies on the more potent compounds showed that Aβ42-lowering steroids were bonafide GSMs and Aβ42-raising steroids were inverse GSMs. The most potent steroid GSM identified was 5β-cholanic acid (EC50=5.7 μM; its endogenous analog lithocholic acid was virtually equipotent), and the most potent inverse GSM identified was 4-androsten-3-one-17β-carboxylic acid ethyl ester (EC50=6.25 μM). In addition, we found that both estrogen and progesterone are weak inverse GSMs with further complex effects on APP processing. These data suggest that certain endogenous steroids may have the potential to act as GSMs and add to the evidence that cholesterol, cholesterol metabolites, and other steroids may play a role in modulating Aβ production and thus risk for AD. They also indicate that acidic steroids might serve as potential therapeutic leads for drug optimization/development.
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Registered trials
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