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Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms
Published on: January 25, 2018
Presenilins and the gamma-secretase: still a complex problem
David H Small1, David W Klaver, Lisa Foa
1Menzies Research Institute, University of Tasmania, Hobart, Tasmania 7001, Australia. d.h.small@menzies.utas.edu.au
Molecular Brain
|February 26, 2010
Summary
Presenilins are key membrane proteins implicated in Alzheimer's disease pathogenesis and amyloid precursor protein metabolism. This review explores their discovery, function, and remaining questions regarding their biochemical actions and calcium ion regulation.
Area of Science:
- Molecular Biology
- Neuroscience
- Biochemistry
Background:
- Presenilins are integral membrane proteins functioning within a larger multi-protein complex.
- This complex is critical for the regulated proteolytic cleavage of various cell-surface and transmembrane proteins.
- Presenilins are strongly linked to the familial forms of Alzheimer's disease.
Purpose of the Study:
- To review the historical discovery and characterization of presenilin proteins.
- To elucidate the role of presenilins in Alzheimer's disease (AD) pathogenesis.
- To examine the biochemical mechanisms and physiological effects of presenilins, including their impact on calcium homeostasis.
Main Methods:
- Literature review of presenilin research.
- Analysis of genetic and biochemical studies related to presenilin function.
- Examination of data concerning amyloid-beta precursor protein (APP) metabolism.
Main Results:
- Presenilins are essential components of the gamma-secretase complex, crucial for APP processing.
- Mutations in presenilins are a major cause of early-onset Alzheimer's disease.
- Presenilins influence intracellular calcium (Ca2+) levels, though the precise mechanisms remain unclear.
Conclusions:
- Presenilins play a pivotal role in both normal cellular function and the pathological processes of Alzheimer's disease.
- Further research is needed to fully understand the enzymatic activity of presenilins and their precise contribution to calcium dysregulation in neurodegenerative diseases.
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