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γ-Secretase inhibitors and modulators for Alzheimer's disease.
- Source :
-
Journal of neurochemistry [J Neurochem] 2012 Jan; Vol. 120 Suppl 1, pp. 89-98. Date of Electronic Publication: 2011 Nov 28. - Publication Year :
- 2012
-
Abstract
- γ-Secretase is a membrane embedded aspartyl protease complex with presenilin as the catalytic component. Along with β-secretase, this enzyme produces the amyloid β-protein of Alzheimer's disease (AD) from the amyloid β-protein precursor. Because of its key role in the pathogenesis of AD, γ-secretase has been a prime target for drug discovery, and many inhibitors of this protease have been developed. The therapeutic potential of these inhibitors is virtually negated by the fact that γ-secretase is an essential part of the Notch signaling pathway, rendering the compounds unacceptably toxic upon chronic exposure. However, these compounds have served as useful chemical tools for biological investigations. In contrast, γ-secretase modulators continue to be of keen interest as possible AD therapeutics. These modulators either shift amyloid β-protein production to shorter, less pathogenic peptides or inhibit the proteolysis of amyloid β-protein precursor selectively compared to that of Notch. The various chemical types of inhibitors and modulators will be discussed, along with their use as probes for basic biology and their potential as AD therapeutics.<br /> (© 2011 The Author. Journal of Neurochemistry © 2011 International Society for Neurochemistry.)
- Subjects :
- Alzheimer Disease metabolism
Animals
Humans
Protease Inhibitors chemistry
Protease Inhibitors pharmacology
Receptors, Notch chemistry
Receptors, Notch physiology
Signal Transduction drug effects
Signal Transduction physiology
Alzheimer Disease drug therapy
Alzheimer Disease enzymology
Amyloid Precursor Protein Secretases antagonists & inhibitors
Amyloid Precursor Protein Secretases physiology
Protease Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 120 Suppl 1
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22122056
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2011.07501.x