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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
Presenilin/gamma-Secretase and Inflammation.
1Institut de Neurociències, Departament Bioquímica i Biologia Molecular, Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona Bellaterra, Spain.
Frontiers in Aging Neuroscience
|June 19, 2010
Summary
Presenilins are key to gamma-secretase, impacting Alzheimer's disease (AD) by processing amyloid precursor protein. Understanding presenilin's role in inflammation and cell signaling offers new therapeutic avenues for AD and other dementias.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Presenilins (PS) are central to gamma-secretase, an enzyme critical for processing signaling proteins.
- Gamma-secretase cleavage of amyloid precursor protein (APP) generates beta-amyloid (Abeta) peptides implicated in Alzheimer's disease (AD) pathogenesis.
- Abeta accumulation disrupts neuronal function, leading to neurodegeneration and cognitive decline.
Purpose of the Study:
- To review evidence on presenilin/gamma-secretase signaling in gliogenesis and gliosis.
- To explore the role of presenilins in neuroinflammation associated with AD and other dementias.
- To identify potential therapeutic targets within the presenilin/gamma-secretase pathway for neurodegenerative diseases.
Main Methods:
- Review of existing literature on presenilin function, gamma-secretase activity, and neuroinflammation.
- Analysis of studies involving presenilin conditional knockout mice and familial AD mutations.
- Examination of the effects of non-steroidal anti-inflammatory drugs on presenilin/gamma-secretase activity.
Main Results:
- Presenilin-1 is crucial for age-dependent Abeta accumulation and neuroinflammation.
- Loss-of-function presenilin mutations are linked to non-AD dementias like frontotemporal dementia.
- Presenilin dysfunction causes neurodegeneration, glial activation, and pro-inflammatory gene induction.
- Anti-inflammatory drugs can modulate PS/gamma-secretase, reducing amyloidogenic Abeta42 levels.
Conclusions:
- Presenilin/gamma-secretase signaling plays a significant role in gliogenesis and gliosis in both normal and pathological brain states.
- Targeting the cellular mechanisms regulated by presenilin/gamma-secretase during inflammation may lead to novel therapeutic strategies for AD.
- Further understanding of presenilin's involvement in neuroinflammation is essential for developing effective treatments for neurodegenerative disorders.
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