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Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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GPCRs Regulate Adenylyl Cylase Activity

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GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
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Regulated Protein Degradation02:58

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Glucagon-like Receptor Agonists

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Related Experiment Video

Updated: May 11, 2026

Quantitative Measurement of &#947;-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms
06:40

Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms

Published on: January 25, 2018

Steroids as γ-secretase modulators.

Joo In Jung1, Thomas B Ladd, Thomas Kukar

  • 1Center for Translational Research in Neurodegenerative Disease and Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 30, 2013
PubMed
Summary
This summary is machine-generated.

Steroids can modulate amyloid-beta 42 (Aβ42) levels, a key factor in Alzheimer's disease (AD). Acidic steroids show potential as gamma-secretase modulators (GSMs) for AD therapy, while non-acidic steroids act as inverse GSMs.

Keywords:
Alzheimer's diseaseAβamyloidcholesterol metabolites

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Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by &#947;-Secretase
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Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase

Published on: June 24, 2025

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Amyloid-beta 42 (Aβ42) aggregation is central to Alzheimer's disease (AD) pathogenesis.
  • Gamma-secretase modulators (GSMs) targeting Aβ42 are a promising therapeutic strategy for AD.
  • Steroids are hypothesized to influence Aβ production, suggesting a potential role in AD risk and treatment.

Purpose of the Study:

  • To screen a library of steroids for their effects on Aβ42 production.
  • To identify specific steroids that can modulate Aβ42 levels via gamma-secretase modulation.
  • To explore the therapeutic potential of steroids in Alzheimer's disease.

Main Methods:

  • Screening of 170 steroids at 10 μM for effects on Aβ42 secretion in human APP-overexpressing cells.
  • Characterization of potent compounds as either GSMs or inverse GSMs.
  • Determination of EC50 values for leading steroid GSMs and inverse GSMs.

Main Results:

  • Acidic steroids were found to lower Aβ42, acting as GSMs.
  • Non-acidic steroids increased Aβ42, functioning as inverse GSMs.
  • 5β-cholanic acid and lithocholic acid were potent GSMs, while a specific androsten derivative was a potent inverse GSM. Estrogen and progesterone showed weak inverse GSM activity.

Conclusions:

  • Certain endogenous steroids possess GSM or inverse GSM activity, influencing Aβ production.
  • Steroids, including cholesterol metabolites, may play a significant role in modulating AD risk.
  • Acidic steroids represent potential therapeutic leads for developing novel Alzheimer's disease treatments.