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The inhibition of gamma-secretase as a therapeutic approach to Alzheimer's disease
Drug News & Perspectives, 2004Alzheimer's disease is a dementing neurodegenerative disorder for which there is no effective treatment at present. Genetic and biological studies provide evidence that the production and deposition of amyloid-beta peptides (Abeta contribute to the etiology of Alzheimer's disease.
Taisuke, Tomita, Takeshi, Iwatsubo
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Gamma Secretase Modulators: New Alzheimer’s Drugs on the Horizon?
Journal of Medicinal Chemistry, 2016The rapidly aging population desperately requires new therapies for Alzheimer's disease. Despite years of pharmaceutical research, limited clinical success has been realized, with several failed disease modification therapies in recent years. On the basis of compelling genetic evidence, the pharmaceutical industry has put a large emphasis on brain beta
Matthew G, Bursavich +2 more
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Current Alzheimer research, 2008
gamma-Secretase is responsible for the final cut of the amyloid beta-peptide (Abeta) precursor (APP) to produce the Abeta peptide implicated the pathogenesis of Alzheimer's disease (AD). Thus, this protease is a top target for the development of AD therapeutics.
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gamma-Secretase is responsible for the final cut of the amyloid beta-peptide (Abeta) precursor (APP) to produce the Abeta peptide implicated the pathogenesis of Alzheimer's disease (AD). Thus, this protease is a top target for the development of AD therapeutics.
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Identity and function of gamma-secretase.
Journal of neuroscience research, 2003gamma-Secretase catalyzes intramembrane proteolysis of various type I membrane proteins, including the amyloid-beta precursor protein and the Notch receptor. Despite its importance in the pathogenesis of Alzheimer's disease and to normal development, this protease has eluded identification until only very recently.
W Taylor, Kimberly, Michael S, Wolfe
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gamma-Secretase in biology and medicine.
Seminars in cell & developmental biology, 2009gamma-Secretase is a membrane-embedded proteolytic complex composed of presenilin and three other subunits. The gamma-secretase complex generates the amyloid beta-peptide of Alzheimer's disease but also plays important roles in normal physiology, especially in signaling from the Notch receptor.
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Advances in gamma-secretase modulation.
Current opinion in drug discovery & development, 2007Inhibition of the production of insoluble amyloid-Beta (ABeta) is a widely pursued strategy for the treatment of Alzheimer's disease (AD). The final step in the generation of ABeta from the amyloid precursor protein (APP) involves cleavage by gamma-secretase, and gamma-secretase inhibitors (GSIs) have been shown to reduce the amyloid burden in animal ...
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An empirical model of gamma-secretase activity.
Annals of the New York Academy of Sciences, 2001gamma-Secretase catalyzes the cleavage at the carboxyl terminus of A beta to release it from the APP. While gamma-secretase is a major therapeutic drug target for the treatment of Alzheimer's disease (AD), it appears to be an unusual proteolytic activity, and, to date, no protease responsible for this activity has been identified.
M P, Murphy +4 more
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Gamma-secretase: never more enigmatic.
Trends in neurosciences, 2002It is widely believed that the pathogenesis of Alzheimer's disease (AD) is intimately, if not causatively, associated with the deposition of approximately 4 kDa beta-amyloid (A beta) peptides in the cerebral cortex and hippocampus of affected individuals. A beta peptides are liberated from transmembrane proteins, termed beta-amyloid precursor proteins (
S S, Sisodia +3 more
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Inhibitors and modulators of beta- and gamma-secretase.
Current topics in medicinal chemistry, 2006Most gene mutations associated with Alzheimer's disease point to the metabolism of amyloid precursor protein as potential cause. The beta- and gamma-secretases are two executioners of amyloid precursor protein processing resulting in amyloid beta. Significant progress has been made in the selective inhibition of both proteases, regardless of structural
Boris, Schmidt +3 more
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Development of Specific Gamma Secretase Inhibitors
2009Secretases are aspartic proteases, which specifically trim important, medically relevant targets such as the amyloid-precursor protein (APP) or the Notch-receptor. Therefore, changes in their activity can lead to dramatic diseases like M. Alzheimer caused by aggregation of peptidic fragments.
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