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Related Experiment Video

Updated: Jun 5, 2025

Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms
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Secretase promotes AD progression: simultaneously cleave Notch and APP.

Ke-Fan Yang1, Jing-Yi Zhang2, Mei Feng1

  • 1Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Shenyang Medical College, Shenyang, China.

Frontiers in Aging Neuroscience
|December 5, 2024
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Summary

Secretases regulate amyloid precursor protein (APP) and Notch pathways, impacting Alzheimer's disease (AD) and cancer. This review details secretase functions and inhibitors for potential therapeutic development in AD and cancer.

Keywords:
ADAPPNotchcancerαβγδεη-secretase

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Alzheimer's disease (AD) pathogenesis involves complex mechanisms.
  • Secretases are proteases regulating key signaling pathways like Notch and amyloid precursor protein (APP).
  • Dysregulation of secretase activity is implicated in AD and cancer progression.

Purpose of the Study:

  • To systematically review the six subtypes of secretases.
  • To elucidate their intracellular localization, cleavage sites, products, and biological functions.
  • To compare commonalities and differences among secretase subtypes.

Main Methods:

  • Systematic review of secretase subtypes (α, β, γ, δ, ε, η).
  • Analysis of their roles in cleaving APP and Notch receptors.
  • Review of secretase inhibitors' chemical structures, indications, and research stages.

Main Results:

  • Secretases cleave APP and Notch, influencing amyloid-beta (Aβ) levels in AD and cancer progression.
  • Each secretase subtype exhibits distinct localization, cleavage specificities, and functional roles.
  • Commonalities and differences among secretase subtypes were identified.

Conclusions:

  • Secretase activity is a critical regulator of APP and Notch pathways in both Alzheimer's disease and cancer.
  • Secretase inhibitors show promise for therapeutic applications in AD and cancer treatment.
  • Further research into secretase mechanisms and inhibitor development is warranted.