Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 72 for “"secretase"”.
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Predicting Substrates of [gamma]-secretase in Drosophila/
… method for predicting substrates of [gamma]-secretase in Drosophila and compared this method with other popular methods using some benchmark data set. Results show our method significantly outperforms other methods and generates important candidates for further experimental validation. …
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Therapeutic Modulation of Experimental Autoimmune Encephalomyelitis by Gamma Secretase Inhibition
… autoimmunity. Small molecule inhibitors of γ-secretase (γSI) have been shown to suppress TH1 differentiation and reduce the severity of experimental autoimmune encephalomyelitis (EAE), presumably by affecting Notch signaling. To understand the mechanisms through which γSI alter autoimmune T …
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Identification and characterization of innate immune receptor substrates of γ-secretase enzyme complex
The γ-secretase protease complexes and associated regulated intramembrane proteolysis play an important role in controlling receptor-mediated intracellular signalling events, which have a central role in Alzheimer’s disease, cancer progression and immune surveillance. It has previously been …
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Intramembrane Proteolysis Mediated by the gamma-Secretase Complex : Nicastrin Functions as a Substrate Receptor
… list of cell signaling events. The gamma -secretase, one of a small family of independently evolved proteases, performs this enigmatic hydrolysis of a peptide bond within the membrane. Remarkably atypical, gamma-secretase activity: (1) requires a complex of proteins that include presenilin, …
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Reconstituting APP and BACE in proteoliposomes to characterize lipid requirements for β-secretase activity
… 2 different (alpha and beta) proteases ("secretases"). The beta-secretase, BACE, cleaves APP in the first step of processing leading to the formation of the neurotoxic Abeta. BACE competes for APP with alpha-secretase, which cleaves APP within its Abeta sequence, thus precluding Abeta …
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Evaluation of selective γ-secretase inhibitors as novel modulators of TNF-α-mediated apoptosis
… characterized as the catalytic subunits of the γ-secretase protease complexes, the presenilins are responsible for the cleavage of the amyloid precursor protein (APP) and generation of amyloid beta (Aβ). To date, γ-secretase proteases have over 120 substrates which demonstrate contribution to a …
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Investigating β- and γ-secretase function and processing of APP with genetic and pharmacological tools
… Precursor Protein (APP) by BACE1 and the gamma secretase complex (γS) generates amyloid-beta (Aβ), a small peptide that is highly implicated in the pathogenesis of Alzheimer’s Disease. Despite decades of research, there remains a lack of understanding of the endogenous functions of APP, BACE1, …
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Sodium dichloroacetate (DCA) impairs β-secretase-mediated proteolysis of the alzheimer's disease amyloid precursor protein (APP)
… of the amyloid precursor protein (APP) by y-secretase yielding soluble APPbeta (sAPPβ) and a membraneassociated C-terminal fragment, C99. The latter fragment is then cleaved by a-secretase liberating the toxic Aβ-peptides. Alternatively, APP can be cleaved non-amyloidogenically by an …
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The racial disparities of the Gamma-secretase/Notch pathway and inhibition in triple negative breast cancer
… disparities, with a specific focus on gamma secretase activity, a key regulator of cellular processes.</p> <p>The research methodology encompasses a multi-faceted approach, amalgamating clinical data analysis with extensive in vitro and in vivo experimentation. The study employs cutting-edge …
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Design and synthesis of novel non peptidomimtic beta-secretase inhibitors in the treatment of Alzheimer's disease
… precursor protein cleaving enzyme, β-secretase) is recognized as one of the most promising targets in the treatment of Alzheimer's disease (AD). The accumulation of β-amyloid peptide (Aβ) in the brain is a major factor in the pathogenesis of AD. Aβ is formed by initial cleavage of …
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Reconstructing the gamma-secretase complex using the MultiBac baculovirus system for expression of heterologous multi-protein complexes
… multi-subunit enzyme complex is referred to as γ-secretase. The enzyme‟s ability to cleave a number of substrates has hampered the development of suitable inhibitors that target γ-secretase with the aim of specifically reducing Aβ production. A clearer understanding of the enzyme‟s structure and …
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GPR50, a potential factor involved in psychiatric disorders interacts with Alzheimer’s disease-related protein β- secretase (BACE1)
… RTN4, SREBP2 and SNX6 are known regulators of β-secretase (BACE1), a key enzyme in Aβ generation, myelination of the central/peripheral nerve, and neurite outgrowth/synapse formation. Preliminary data indicated that GPR50 expression significantly increased endogenous BACE1 activity in HEK293 …
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Development of a beta-Secretase Activated Prochelator and FRET Probe to Mediate Copper Toxicity in Alzheimer's Disease
… system, SWH to CP conversion is mediated by beta-secretase, an enzyme involved in A-beta generation. However, in order to render SWH capable of hydrolysis in cells, we modified the prochelator to contain a dihydrocholesterol membrane anchor attached via a polyethylene glycol linker. From this …
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Analysis of gamma secretase regulation by phosphatidylethanolamine using mammalian and Drosophila melanogaster in vitro and in vivo model systems
… the amyloid precursor protein (APP) by ?- and ?-secretase. APP is additionally processed through a non-amyloidogenic pathway by ?-secretase. Recent work suggests that amyloidogenesis is highly dependent on the levels of cholesterol within plasma membrane/early endosomes’ microdomains termed …
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FKBP14 in Notch Signalling and Drosophila Development
… that form the catalytic core of the gamma-secretase complex, which cleaves a growing list of transmembrane proteins including Notch and Amyloid Precursor Protein. Autosomal dominant mutations in the genes encoding human PS have been closely linked to cases of early onset familial …
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Investigation of p75 neurotrophin receptor and the role of its post-translational modifications in tumour cell motility and invasiveness
… Recently,p75NTR was also shown to undergo γ-secretase-mediated regulated intramembrane proteolysis, and the receptor ICD was found to migrate to the nucleus where it regulates gene transcription. Moreover, γ-secretase-mediated proteolysis was shown to be involved in glioblastoma cell …
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The Processing of Amyloid Precursor Protein in the Central Nervous System of Humans and Rhesus Macaques
… If APP is processed down the amyloidogenic: β-secretase) pathway, soluble APPβ: sAPPβ) will be released first, and with a subsequent cleavage, β-amyloid: Aβ), will be released into the brain where it could sequester into amyloid plaques, which are a major hallmark of AD. The other processing …
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Amyloid precursor protein subtypes and secretases implicated in Alzheimer's disease.
… APP[751]; APP[695]; ADAM 9, 10 and 17 as alpha-secretases; BACE 1 as beta-secretase and PS1 as gamma-secretase.The APP[695] isoform was found to have the highest levels in the frontal and temporal regions. However, the APP[751] isoform was found to be at the highest level, with very low levels …
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Interrogating regulated intramembrane proteolysis of IGF-1R, and its role in cell migration
… has been characterised as a substrate for gamma-secretase-mediated regulated intramembrane proteolysis (RIP). This proteolytic pathway begins with ectodomain shedding, mediated by sheddases, which produces a soluble fragment in the extracellular space. Following ectodomain shedding, a membrane …
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Analysis of the subcellular localization of proteins implicated in Alzheimer’s disease
… PRECURSOR PROTEIN (APP) by the enzyme complex γ-secretase. The catalytic component of the γ-secretase complex is PRESENILIN (PSEN1 or PSEN2). Mutations in the human PSEN1 gene have been identified in AD. Some mutations have been found to cause frame shifts leading to premature stop codons that …
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