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Updated: Jun 25, 2026
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
The γ-secretase complex: from discovery to a therapeutic target
Shweta R Malvankar1, Michael S Wolfe1
1Department of Medicinal Chemistry, School of Pharmacy, The University of Kansas 1567 Irving Hill Road, GLH 2215 Lawrence KS 66045 USA mswolfe@ku.edu.
RSC Chemical Biology
|June 24, 2026
Summary
Gamma-secretase, a membrane-bound protease, processes numerous substrates, including amyloid precursor protein. This review explores its role in diseases like Alzheimer's and its therapeutic potential.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Gamma-secretase is a critical intramembrane aspartyl protease involved in cleaving transmembrane domains.
- It comprises four subunits, with presenilin serving as the catalytic component.
- Often referred to as the 'proteasome of the membrane,' it processes approximately 150 substrates.
Purpose of the Study:
- To provide a comprehensive overview of gamma-secretase's biochemistry and biology.
- To discuss its involvement in human diseases, particularly Alzheimer's disease.
- To evaluate gamma-secretase as a therapeutic target.
Main Methods:
- Literature review focusing on gamma-secretase discovery, structure, and function.
- Analysis of gamma-secretase substrates, including amyloid precursor protein and Notch1.
- Examination of substrate processing, sequence specificity, and pathological roles.
Main Results:
- Detailed discussion on the discovery and structural characteristics of gamma-secretase.
- Survey of key substrates and their processing mechanisms.
- Exploration of gamma-secretase's role in Alzheimer's disease pathogenesis and the controversy surrounding amyloid-beta peptide.
Conclusions:
- Gamma-secretase is a vital enzyme with significant implications in human health and disease.
- Its role in Alzheimer's disease warrants further investigation, especially regarding amyloid-beta.
- Gamma-secretase inhibitors and modulators show promise as therapeutic strategies for various diseases.
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