-Secretase
Pharmacological Assessment of γ Secretase Activity from Rodent and Human Brain
... Two different classes of pharmacological agents, γ- secretase inhibitors (GSIs) and γ-secretase modulators (GSMs), affect γ-secretase activity in mechanistically distinct ways [18,19]. GSIs inhibit ...
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Peripheral and central effects of γ-secretase inhibition by semagacestat in Alzheimer’s disease
... Analysis of the relationships among PK/pharmacody- namic measures, biomarkers and laboratory tests in the phase III trial of semagacestat in mild to moderate AD provides some insight into the neurobiological and clin- ...
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Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors
... gamma secretase at the aqueous surface of the membrane where protease activity is also speculated to occur ...gamma secretase, are intramembrane peptidases that are sensitive to com- pounds that affect ...
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Cholestenoic acid, an endogenous cholesterol metabolite, is a potent γ-secretase modulator
... There have been studies demonstrating that production and processing of Aβ can be influenced by membrane lipid composition [18–21]. In particular, membrane chol- esterol appears to play an important role [18]. APP-CTFβ ...
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NSAIDs and enantiomers of flurbiprofen target γ secretase and lower Aβ42 in vivo
... A drawback to the potential clinical use of conven- tional NSAIDs in AD, either as Aβ42 lowering agents or as anti-inflammatory medications, is the gastroin- testinal and renal toxicity thought to be mediated by their ...
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Wang, Huanhuan (2012): Identification of the physiologically relevant α-secretase of the Alzheimer’s disease-related amyloid precursor protein and its relationship with β-secretase. Dissertation, LMU München: Medizinische Fakultät
... The amyloid precursor protein (APP) is one of a large number of membrane proteins that are proteolytically converted to their soluble counterparts. This process is referred to as ectodomain shedding and is an important ...
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BACE2, a conditional β-secretase, contributes to Alzheimer’s disease pathogenesis
... It is also interesting to note that overexpressed BACE1 and endogenous α-secretase only cleave mature APP after ER export. Since there is always sufficient APP, both mature and immature, in the brain (see ...
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Modulation of Aβ42 in vivo by γ-secretase modulator in primates and humans
... approximately 200 nM, compared to 250–500 μM for ibu- profen (Fig. 1). Although not reported for GSM-1, a GSM with similar structure and comparable in vitro and in vivo GSM activity, GSM-10 h, demonstrated excellent ...
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Autophagy dysfunction upregulates beta-amyloid peptides via enhancing the activity of γ-secretase complex
... Notes: columns depict relative densitometric values that were obtained by comparing with β-actin. Presenilin 1, Nicastrin, and Pen-2 were increased with the 3-Ma treatment (*P , 0.001) while the other component of the ...
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Beta-Secretase 1 (BACE1) Is Down-Regulated in Invasive Ductal Carcinoma of Breast
... In the present study we evaluated BACE1 and BACE1-AS expression in invasive ductal carcinoma of breast and found significantly less BACE1 in tumors than in ANCTs. BACE1 catalyzes the primary step of APP production (1), ...
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An exo-cell assay for examining real-time γ-secretase activity and inhibition
... γ-Secretase is an aspartyl protease that cleaves multiple substrates that are involved in broad biological processes ranging from stem cell development to neurodegeneration. The investigation of γ-secretase ...
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Original Article Evaluation of clinical efficacy of α-secretase in the treatment of Alzheimer’s disease
... In this study, a randomized controlled trial of 134 patients with AD was conducted, used two different drugs and evaluated the recovery of the patients. The two groups of patients’ reac- tion ability and intelligence ...
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Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease
... It is noteworthy that all substrate selective GSIs described to date are based on sulfonamide phar- macophore ([47,79,85-87], and this report). Indeed, a first generation aryl sulfonamide GSI, BMS299897 [10,11,88], was ...
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A novel Aβ isoform pattern in CSF reflects γ-secretase inhibition in Alzheimer disease
... Intense multidisciplinary research efforts during the last decades have provided detailed knowledge on the molecular pathogenesis of AD, which has been translated into novel promising therapies with putative disease- ...
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Shrimp (Pandalopsis dispar) waste hydrolysate as a source of novel β–secretase inhibitors
... Phe–His acted competitively according to the Linewea- ver–Burk plot (data not shown). In both peptides (Asp– Val–Leu–Phe–His and Leu–Phe–His), leucine is likely to be the important residue for β–secretase ...
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Sortilin, SorCS1b, and SorLA Vps10p sorting receptors, are novel γ-secretase substrates
... Because of their topologic similarity to other γ-secretase substrates and evidence for ectodomain shedding [42] (Figure 1a), we hypothesized that the mammalian Vps10p containing family of proteins might be ...
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APLP1 as a cerebrospinal fluid biomarker for γ-secretase modulator treatment
... these effects, γ -secretase modulators (GSMs) have been developed, which rather than inhibiting γ -secretase shift its preference into producing less aggregation-prone shorter A β peptides. Belonging to the ...
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Papillomavirus Infection Requires γ Secretase
... ␥ secretase are typically precut with a proprotein convertase at a position less than 30 residues from the transmembrane domain to reveal a free amine to facilitate NCT recognition ...␥ secretase are within ...
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Quantification of gamma-secretase modulation differentiates inhibitor compound selectivity between two substrates Notch and amyloid precursor protein
... Genetic and neuropathologic evidence suggests that Alzheimer's disease (AD) is caused partly by the overpro- duction and lack of clearance of the amyloid β peptide (Aβ) [1]. This Aβ peptide is generated by sequential ...
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Targeting γ-secretase in breast cancer
... lines are responsive to GSI treatment, the expression and/or activity of the γ -secretase substrates, whose reduced cleavage by GSI treatment provides prosurvival/proliferation signal in the GSI nonresponsive ...
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