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Target intelligence / Profile preview
Gamma-Secretase Complex (γ-Secretase)
- Target
- γ-Secretase
- Molecular classification
- Protease, Enzyme, Multi-subunit protein complex
01
Overview
The gamma-secretase complex is a multi-subunit, membrane-embedded protease responsible for the intramembrane cleavage of various type I transmembrane proteins, including amyloid precursor protein (APP) and Notch receptors. It consists of four essential subunits: Presenilin (PSEN1 or PSEN2), Nicastrin, Anterior Pharynx Defective-1 (APH-1), and Presenilin Enhancer Protein 2 (PEN-2). The complex plays crucial roles in cell signaling, development, and neurodegenerative diseases, particularly Alzheimer's disease.
- Other names
- Gamma Secretaseγ Secretase
02
Mechanism of action
Gamma-secretase inhibitors block the proteolytic activity of the complex, preventing cleavage of APP and Notch, which is a mechanism tested in clinical trials.
03
Biological functions
Intramembrane proteolysisAPP processingNotch signalingSignal transduction
04
Disease associations
Alzheimer's diseaseDevelopmental disorders
05
Safety considerations
Worsening of cognitive function (clinical trials)Skin cancer (clinical trials)Gastrointestinal side effects
06
Interacting drugs
Semagacestat
2 more in the full profile.
07
Biomarkers
Amyloid-beta 42 (Aβ42) levelsAmyloid plaques (imaging)Cerebrospinal fluid (CSF) Aβ42/Aβ40 ratio
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