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 25 for “"γ-secretase"”.
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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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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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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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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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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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Notch Signaling in Neuroblastoma and Renal Cell Carcinoma
… with daily injections of a Notch inhibitor (γ-secretase inhibitor) in cycles of 3 days followed by 4 days without treatment, retarded tumor growth and minimized the adverse effects commonly associated with γ-secretase inhibition. In addition, analysis of primary CCRCC samples revealed that …
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Novel Mechanisms of Antigen Processing That Enhance Bcg Vaccine Efficacy
… led to the discovery of novel protease (γ-secretase) enriched on BCG vaccine phagosomes. We then demonstrated that these proteases generated a peptide from the BCG vaccine which was presented through the MHC-II pathway to T cells and induced a T<sub>H</sub>1 response. The specificity of …
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Modification of Lipid Microenvironments on Solid Support Structures for Use in Transmembrane Protein Assays
<p>Gamma-Secretase (γ-secretase) is a transmembrane protease of increasing interest, which has been shown to have significant connections to both cancer and Alzheimer’s disease. γ-secretase cleaves both Notch-1, a transmembrane signaling protein, and Amyloid precursor protein (APP), a transmembrane …
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Analysing the biological function of PS2V: an aberrant splicing phenomenon or evolutionarily conserved mechanism in Alzheimer’s disease
… different types of aspartyl proteases, β- and γ-secretase. The majorities of AD cases are sporadic and have a late onset. Mutations in genes encoding APP, PRESENILIN1 and 2 (PSEN1 and PSEN2) cause an autosomal dominant inherited form of the disease with an early onset known as familial AD. In …
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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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The Effects Of Oxidative Stress On P75ntr Signaling In Dopaminergic Neurons
… Necrosis Factor converting enzyme (TACE) and γ-secretase has been observed to be associated with an increase in neurodegeneration. In a previous study, p75NTR was discovered to become activated in sympathetic neurons in response to oxidative stress induced by 4-hydroxynonenal (HNE) in a …
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Driver genes associated to Broad Copy Number Aberrations in solid cancers
… enhanceosome components), APH1A, PSEN2, NCSTN (γ-secretase subunits), and CDH1 (involved in cell adhesion). The bioinformatics results were verified on cell models bearing chr 1/16 aberration (CAL148) or not bearing it (CAL51). We performed siRNA interfering and pharmacological experiments …
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Accelerated simulations and computer-aided drug design of membrane proteins
… and Pep-GaMD to determine the mechanisms of γ-secretase activation and substrate processive proteolysis. In Chapters 3 and 4, I focus on investigating the dependence of GPCR-membrane interactions on the receptor activation state and retrospective docking of known positive allosteric modulators …
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Characterization of a novel interaction between presenilin-1 and monoamine oxidase-A
… following in vitro chemical inhibition of the γ-secretase complex (comprising several proteins including PS-1) support the notion that PS-1 constitutively associates with MAO-A. These effects on Ca²⁺-sensitive MAO function could contribute to AD-related pathology and could also contribute to the …
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A study of Notch signalling in developmental angiogenesis
… signalling by pharmacological inhibition of γ-secretase or genetic deletion of one Dll4 allele resulted in excessive endothelial tip cell formation and a poorly-patterned, hyperdense vessel network. Induction of Notch signalling by Jagged1 peptide treatment led to a decrease in tip cell …
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Investigating the genome of Anaplastic Lymphoma Kinase-positive Anaplastic Large Cell Lymphoma
… of notch1. Moreover, inhibition of Notch1 with γ-secretase inhibitors (GSI) or silencing by shRNA leads to apoptosis; co-treatment in vitro with the ALK inhibitor crizotinib led to additive/synergistic anti-tumour activity suggesting this may be an appropriate combination therapy for future use in …
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Presenilins Modulate Cellular Activity of Ryanodine Receptors
… signaling, and act as the proteolytic core of γ-secretase in amyloid cleavage. Previous single channel electrophysiology studies described a direct interaction between RyR and the N-termini of presenilin 1 (PS1NTF) and presenilin 2 (PS2NTF) that resulted in differential modulation of the RyR open …
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Anti-Tumor Effects of The Notch Pathway In Gastrointestinal Stromal Tumors
… inhibition of Notch pathway with a γ-secretase inhibitor partially rescued GIST cells from SAHA treatment.</p> <p>Taken together these results identify anti-tumor effect of <em>Notch1</em> and a negative cross-talk between Notch1 and KIT pathways in GIST<em>. </em>Consequently, we …
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Multiomic Analyses Reveal Epigenomic Alterations and New Targets of Polycomb Repressive Complex 2 in Schwann Lineage Cells and Malignant Peripheral Nerve Sheath Tumors
… PRC2-deficient cells. A combination of MEK and γ-secretase inhibition showed synergy in MPNST cell lines. We identified PRC2-regulated genes and potential drivers of MPNSTs. Our identification of PRC2-regulated genes and pathways could result in more novel therapeutic approaches. In our third …
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