Results 171 to 180 of about 38,664 (219)

γ-Secretase: proteasome of the membrane?

Nature Reviews Molecular Cell Biology, 2004
γ-Secretase — a protease that cleaves within the membrane — was first recognized for its role in the production of amyloidogenic Aβ peptides, but was subsequently found to mediate Notch signalling by releasing the Notch-receptor intracellular domain. Many other γ-secretase substrates have recently been identified, which indicates a broader biological ...
Raphaël Kopan, Ma Xenia G Ilagan, Kopan Raphaël   +2 more
exaly   +3 more sources

The secretases of Alzheimer's disease

2003
Publisher Summary Only a few years ago, the proteases responsible for the processing of amyloid-β precursor protein (APP) were completely unknown, hampering efforts to understand the molecular basis of Alzheimer's disease (AD) and develop effective therapeutic agents.
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Structure and function of γ-secretase

Seminars in Cell & Developmental Biology, 2009
The gamma-secretase complex is a prime target for pharmacological intervention in Alzheimer's disease and so far drug discovery efforts have yielded a large variety of potent and rather specific inhibitors of this enzymatic activity. However, as gamma-secretase is able to cleave a wide variety of physiological important substrates, the real challenge ...
Alexandra, Tolia, Bart, De Strooper
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Identification and biology of α‐secretase

Journal of Neurochemistry, 2011
J. Neurochem.(2012)120(Suppl. 1), 34–45.Absract‘Secretase’ is a generic term coined more than 20 years ago to refer to a group of proteases responsible for the cleavage of a vast number of membrane proteins. These endoproteolytic events result in the extracellular or intracellular release of soluble metabolites associated with a broad range of ...
Valérie, Vingtdeux, Philippe, Marambaud
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Substrate recruitment by γ-secretase

Seminars in Cell & Developmental Biology, 2020
γ-Secretase is a membrane-embedded protease complex that is crucial for many physiological processes throughout life. Due to its pivotal role in the etiology of Alzheimer's disease (AD), in particular the familial forms of the disease, the enzyme is one of the most studied intramembrane proteases and an important drug target.
Fukumori, Akio, Feilen, Lukas P, Steiner, Harald   +2 more
openaire   +3 more sources

Aminothiazoles as γ-secretase modulators

Bioorganic & Medicinal Chemistry Letters, 2011
We herein report the discovery of a new γ-secretase modulator class with an aminothiazole core starting from a HTS hit (3). Synthesis and SAR of this series are discussed. These novel compounds demonstrate moderate to good in vitro potency in inhibiting amyloid beta (Aβ) peptide production.
Thomas, Lübbers, Alexander, Flohr, Synese, Jolidon, Pascale, David-Pierson, Helmut, Jacobsen, Laurence, Ozmen, Karlheinz, Baumann   +6 more
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γ-Secretase: Substrates and Inhibitors

Molecular Neurobiology, 2002
The amyloid beta-protein (Abeta) deposited in Alzheimer's disease (AD), the most common form of dementia in the elderly, is a secreted proteolytic product of the amyloid beta-protein precursor (APP). Generation of Abeta from the APP requires two sequential proteolytic events, beta-secretase cleavage to generate the amino terminus, followed by gamma ...
Marjorie J, Rochette, M Paul, Murphy
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Iminoheterocycles as γ-secretase modulators

Bioorganic & Medicinal Chemistry Letters, 2010
The synthesis of a novel series of iminoheterocycles and their structure-activity relationship (SAR) as modulators of gamma-secretase activity will be detailed. Encouraging SAR generated from a monocyclic core led to a structurally unique bicyclic core.
John P, Caldwell, Chad E, Bennett, Troy M, McCracken, Robert D, Mazzola, Thomas, Bara, Alexei, Buevich, Duane A, Burnett, Inhou, Chu, Mary, Cohen-Williams, Hubert, Josein, Lynn, Hyde, Julie, Lee, Brian, McKittrick, Lixin, Song, Giuseppe, Terracina, Johannes, Voigt, Lili, Zhang, Zhaoning, Zhu   +17 more
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Triazoles as γ-secretase modulators

Bioorganic & Medicinal Chemistry Letters, 2011
Synthesis, SAR, and evaluation of aryl triazoles as novel gamma secretase modulators (GSMs) are presented in this communication. Starting from the literature and in-house leads, we evaluated a range of five-membered heterocycles as replacements for olefins commonly found in non-acid GSMs.
Christian, Fischer, Susan L, Zultanski, Hua, Zhou, Joey L, Methot, W Colby, Brown, Dawn M, Mampreian, Adam J, Schell, Sanjiv, Shah, Hugh, Nuthall, Bethany L, Hughes, Nadja, Smotrov, Candia M, Kenific, Jonathan C, Cruz, Deborah, Walker, Melanie, Bouthillette, George N, Nikov, Dan F, Savage, Valentina V, Jeliazkova-Mecheva, Damaris, Diaz, Alexander A, Szewczak, Nathan, Bays, Richard E, Middleton, Benito, Munoz, Mark S, Shearman   +23 more
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Dissecting γ‐secretase function

Journal of Neurochemistry, 2013
Read the full article ‘Important functional role of residue x of the presenilin GxGD protease active site motif for APP substrate cleavage specificity and substrate selectivity of γ‐secretase’ on doi: 10.1111/jnc.12124.
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