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γ-Secretase in Alzheimer’s disease
Alzheimer’s disease (AD) is caused by synaptic and neuronal loss in the brain. One of the characteristic hallmarks of AD is senile plaques containing...
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Microbial infection promotes amyloid pathology in a mouse model of Alzheimer’s disease via modulating γ-secretase
Microbial infection as a type of environmental risk factors is considered to be associated with long-term increased risk of dementia, including...
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Presenilin/γ-Secretase in the Pathogenesis of Alzheimer’s Disease
A genetic study of familial cases of Alzheimer’s disease (AD)Alzheimer’s disease (AD) has revealed that amyloid-βAmyloid-β protein (Aβ) is an...
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Enzyme-substrate hybrid β-sheet controls geometry and water access to the γ-secretase active site
γ-Secretase is an aspartyl intramembrane protease that cleaves the amyloid precursor protein (APP) involved in Alzheimer’s disease pathology and...
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Effects of presenilin-1 familial Alzheimer’s disease mutations on γ-secretase activation for cleavage of amyloid precursor protein
Presenilin-1 (PS1) is the catalytic subunit of γ-secretase which cleaves within the transmembrane domain of over 150 peptide substrates. Dominant...
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CNTNAP2 intracellular domain (CICD) generated by γ-secretase cleavage improves autism-related behaviors
As the most prevalent neurodevelopmental disorders in children, autism spectrum disorders (ASD) are characterized by deficits in language...
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Cooperation of N- and C-terminal substrate transmembrane domain segments in intramembrane proteolysis by γ-secretase
Intramembrane proteases play a pivotal role in biology and medicine, but how these proteases decode cleavability of a substrate transmembrane (TM)...
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A thermodynamic investigation of amyloid precursor protein processing by human γ-secretase
Human γ-secretase cleaves the transmembrane domains (TMDs) of amyloid precursor protein (APP) into pathologically relevant amyloid-β peptides (Aβs)....
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Hypoxia Inducible Factor-1α binds and activates γ-secretase for Aβ production under hypoxia and cerebral hypoperfusion
Hypoxic-ischemic injury has been linked with increased risk for develo** Alzheimer’s disease (AD). The underlying mechanism of this association is...
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Turning the tide on Alzheimer’s disease: modulation of γ-secretase
Alzheimer’s disease (AD) is the most common type of neurodegenerative disorder. Amyloid-beta (Aβ) plaques are integral to the “amyloid hypothesis,”...
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Oxidative stress-induced MMP- and γ-secretase-dependent VE-cadherin processing is modulated by the proteasome and BMP9/10
Classical cadherins, including vascular endothelial (VE)-cadherin, are targeted by matrix metalloproteinases (MMPs) and γ-secretase during adherens...
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Molecular pathogenesis of desmoid tumor and the role of γ-secretase inhibition
Desmoid tumor (DT) is a rare, soft tissue neoplasm associated with an unpredictable clinical course. Although lacking metastatic potential, DT is...
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Nanoscale organization of Nicastrin, the substrate receptor of the γ-secretase complex, as independent molecular domains
Alterations in the canonical processing of Amyloid Precursor Protein generate proteoforms that contribute to the onset of Alzheimer’s Disease....
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Apo and Aβ46-bound γ-secretase structures provide insights into amyloid-β processing by the APH-1B isoform
Deposition of amyloid-β (Aβ) peptides in the brain is a hallmark of Alzheimer’s disease. Aβs are generated through sequential proteolysis of the...
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The evolved divergence of γ-secretase-susceptibility of homologous proteins Ngfrb and Nradd in zebrafish
ObjectiveNGFR/p75NTR and NRADD/NRH proteins are closely related structurally and are encoded by genes that arose from a duplication event early in...
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Targeting γ-secretase for familial Alzheimer’s disease
Familial Alzheimer’s disease (FAD) is a rare early-onset genetic form of common dementia of old age. Striking in middle age, FAD is caused by...
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Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex
Ciclopirox (CPX) is an FDA-approved topical antifungal agent that has demonstrated preclinical anticancer activity in a number of solid and...
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Class II phosphatidylinositol 3-kinase-C2α is essential for Notch signaling by regulating the endocytosis of γ-secretase in endothelial cells
The class II α-isoform of phosphatidylinositol 3-kinase (PI3K-C2α) plays a crucial role in angiogenesis at least in part through participating in...
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The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer’s disease
Innate immunity is associated with Alzheimer’s disease
1 , but the influence of immune activation on the production of amyloid-β is unknown2 ,3 . Here we...