Global ETD Search
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Showing 1 to 20 of 39 for “"Presenilin"”.
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Novel Optical Tools to Investigate Presenilin Control of Neurotransmission
… we investigate the controversial hypothesis that Presenilins are ER Ca<sup>2+</sup> leak channels to determine if a role in ER Ca<sup>2+</sup> leak can explain the previously described regulation of neurotransmission by Presenilins. While Presenilins are best known for their involvement in …
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Characterization of a novel interaction between presenilin-1 and monoamine oxidase-A
… been linked to gain-of-function mutations in the presenilin-1 (PS-1) protein that not only promote the generation of the toxic amyloid-β peptide, but that also alter intracellular Ca²⁺ availability. Radioenzymatic MAO assays were used to demonstrate that over-expression of different AD-related …
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Vergleichende Untersuchung des Reelinsignalweges bei Wildtyp- und Presenilin-1-Knockoutmäusen während der embryonalen Hirnentwicklung
Ein Defekt im Presenilin-1-Gen führt zum Phänotyp der Lissenzephalie Typ 2. Es ist bekannt, dass die Reelinexpression in Presenilin-1-Knockoutmäusen vermindert ist. In dieser Arbeit wurde untersucht, ob der Reelin-Dab1-Signaltransduktionsweg ebenfalls beeinflusst ist. Dazu wurden die Veränderungen …
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Charakterisierung des mit der Alzheimer Krankheit assoziierten Genprodukts Presenilin 1 und Interaktion mit beta-Catenin
… Fragestellungen bearbeitet, die sich auf das Presenilin 1 Protein allgemein, auf dessen Prozessierung zu C- und N-terminalen Fragmenten und die physiologisch vorliegende Form als Heterodimer bezogen. Es wurde untersucht, unter welchen Bedingungen sich Volllängen-PS1 Protein und PS1-Fragmente …
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Differenzielle Effekte von Presenilin-Mutationen auf die Generierung des Amyloid-ß-Peptids (Aß) und die Endoproteolyse des Notch-Rezeptors
… disease cases are caused by mutations in the presenilin genes, PS1 and PS2. PS mutations result in the enhanced production of the highly amyloidogenic 42/43 amino acid variant of amyloid ß-peptide (Aß). Arbitrary mutations were introduced at position 286 of PS1, where a naturally occurring PS1 …
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Evaluation of selective γ-secretase inhibitors as novel modulators of TNF-α-mediated apoptosis
The presenilin proteins (presenilin 1 and presenilin 2) were identified in mutagenesis screens causing the early onset forms of familial Alzheimer’s disease (FAD) in 1995. Subsequently characterized as the catalytic subunits of the γ-secretase protease complexes, the presenilins are responsible for …
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Analysis and suppression of mutant sel-12 in Caenorhabditis elegans
… and functionally homologous to the human presenilins, PS1 and PS2. Mutations in the human presenilins contribute to the majority of familial Alzheimer's disease cases. Work in C. elegans also revealed that presenilins are involved in Notch signaling as a reduction of sel-12 presenilin …
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Modeling Alzheimer's Disease Using CRISPR/CAS9 Gene Editing and Induced Pluripotent Stem Cells Reveals Conserved Cellular Mechanisms
… (APP), and two APP processing-related genes (presenilin-1 (PSEN1), and presenilin-2 (PSEN2)), supporting the theory that altered APP metabolism is a central cause of AD. However, which product of APP metabolism is causal remains a matter of investigation. A probable source of this lack of …
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Familial Alzheimer's Disease Mutations in Presenilins Disrupt Endoplasmic Reticulum Calcium Leak
… factors for developing AD are age, mutations in presenilins (PS1 and PS2), mutations in the amyloid precursor protein (APP), cardiovascular diseases, open heart surgery, diabetes, brain injury/head trauma, Apolipoprotein E-e4 (APOE-e4) and the (P86L) mutation in the CALHM1(Calcium homeostasis …
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Predicting Substrates of [gamma]-secretase in Drosophila/
… common hypotheses for Alzheimer's disease: the presenilin hypothesis and amyloid hypothesis.
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FKBP14 in Notch Signalling and Drosophila Development
Presenilins (PSs) are highly conserved transmembrane proteins 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 …
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Modulation of neuronal ryanodine receptor-mediated calcium signaling by calsenilin
… in early-onset familial Alzheimer disease (AD), presenilin 1 and presenilin 2. Several studies have shown overexpression of calsenilin to alter Ca2+ signaling and cell viability in several neuronal cell models of AD. In this study, we show that calsenilin directly interacts with the ryanodine …
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Presenilins Modulate Cellular Activity of Ryanodine Receptors
Payne, Andrew J., Presenilins Modulate Cellular Activity of Ryanodine Receptors. Doctor of Philosophy (Biomedical Sciences), December, 2012, 160 pp., 7 tables, 39 figures, bibliography 241 titles. Ryanodine Receptors (RyRs) are large, endoplasmic reticulum (ER) intracellular calcium channels in …
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Untersuchung zur intrazellulären Ca 2+ -Homöostase an hippokampalen Neuronen von PS1- und App-Maus-Mutanten
Mutationen in den Genen Presenilin 1 und 2 (PS1, PS2) sowie im Amyloid-Precursor-protein (App)gehen mit der autosomal-dominant vererbten Alzheimer Krankheit einher. In neuronalen Zellen von Mäusen, die eine PS1-Mutation tragen, löst eine derartige Mutation eine verstärkte Ca 2+ -Freisetzung aus dem …
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Intramembrane Proteolysis Mediated by the gamma-Secretase Complex : Nicastrin Functions as a Substrate Receptor
… (1) requires a complex of proteins that include presenilin, nicastrin, Aph1, and Pen-2; (2) catalyzes the intramembrane cleavage of a broad range of substrates, regulating physiology from neurodevelopment to neurodegeneration. The aim of this thesis is to elucidate the mechanism by which the …
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Modeling Alzheimer's Disease in Induced Pluripotent Stem Cells
… key genes: amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN-2). Together, these pathologic findings and genetics provided the framework for the amyloid cascade hypothesis, which states that Aβ deposition is a necessary, early event that is upstream of the …
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Regulators of autophagy in Leishmania major
… interactions. To analyse the role of a predicted presenilin-1 (PS1) homologue in L. major, Δps1 null mutants were generated. These mutants were not defective in their ability to differentiate into infective metacyclic promastigotes, and could establish infections in vivo and in vitro, …
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Reconstructing the gamma-secretase complex using the MultiBac baculovirus system for expression of heterologous multi-protein complexes
… γ-secretase activity. Four core proteins, namely Presenilin (PS), Nicastrin (NCT), Anterior-pharynx defective homolog-1 (aph1aL/ aph1aS/ aph1b) and Presenilin enhancer-2 (pen2), interact to form the active γ-secretase complex. The assembly and function of the enzyme components are slowly becoming …
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