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 21 for “"BACE1"”.
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The hypothalamic role of BACE1 in energy homeostasis
… amyloid precursor protein-cleaving enzyme 1 (BACE1) is critically involved in AD development, cleaving the amyloid precursor protein (APP) to generate amyloid-β (Aβ), which drives progression of the hallmark pathologies of AD. Consequently, higher BACE1 levels/activity is considered a primary …
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The role of peripheral BACE1 in modulating metabolic health
… protein (APP) by β-site APP cleaving enzyme 1 (BACE1). BACE1 is an aspartyl protease which is up-regulated by a number of cellular stresses, including hypoxia and metabolic stress, such as with high fat diet (HFD). This led to the suggestion that BACE1 may play a role in energy homeostasis. …
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Regulation of BACE1 promoter activity by nuclear factor-kappaB\r\n
… (APP). The beta-site APP-cleaving enzyme 1 (BACE1) is required for the generation of beta-amyloid peptides. The NF-kappaB binding DNA consensus sequence in the BACE1 promoter upstream of the gene’s transcription start site suggests a role for NF-kappaB in the expression of neuronal brain …
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Investigating the physiological function of BACE1 and its role in metabolism
… amyloid precursor protein cleaving enzyme 1 (BACE1). Whilst the function of this enzyme has been well studied within the context of AD, very little is known about its physiological function within healthy organisms. However, studies have identified that BACE1 KO mice are resistant to …
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Investigation of BACE1 as a stress-induced regulator of neuronal metabolism
… precursor protein (APP) cleaving enzyme 1 (BACE1), the rate-limiting step in A production is currently of great therapeutic interest. With the prevailing view being that reducing BACE1 levels will be beneficial in AD, there remains a need to better understand the physiological roles of …
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Investigating nutrient excess and endothelial dysfunction: a role for BACE1 and amyloid?
… lengths by beta-site APP cleaving enzyme 1 (BACE1). Increased circulating Aβ42 levels is reported to promote ED, by reducing NO bioavailability, suggesting a role for Aβ in the pathogenesis of ED, but the underlying mechanism is unclear. <br/><br/>One potential mechanism involves …
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Investigation of the role of BACE1 in adipocyte and immune cell function
… upon cleavage by an aspartyl protease named BACE1 (β-site amyloid precursor protein cleaving enzyme 1). This enzyme is the rate-limiting enzyme involved in the cleavage of amyloid precursor protein (APP) which, followed by γ-secretase cleavage, results in amyloid (or Aβ) peptide formation …
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GPR50, a potential factor involved in psychiatric disorders interacts with Alzheimer’s disease-related protein β- secretase (BACE1)
… 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 cells, so I …
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Design and synthesis of novel non peptidomimtic beta-secretase inhibitors in the treatment of Alzheimer's disease
The aspartic protease BACE1 (β-amyloid 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 …
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Investigating β- and γ-secretase function and processing of APP with genetic and pharmacological tools
… cleavage of Amyloid 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 …
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Hiv And Antiretrovirals In The Central Nervous System: Molecular Mechanisms Of Cognitive Impairment
… amyloid precursor protein cleaving enzyme 1 (BACE1), which may play a role in the onset and progression of Alzheimer’s Disease, was both increased in HIV+ patient brains and required for HIV-associated neurotoxicity in vitro. The BACE1 cleavage target amyloid precursor protein (APP) also …
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Mechanisms Regulating Amyloid Processing Enzymes in HIV-Associated Neurotoxicity
… precursor protein (APP) by the secretases BACE1, are observed in the brains of HAND. Aβ production is precluded by cleavage of APP by the non-amyloidogenic secretase ADAM10. BACE1 is increased in HAND as well as in our cell culture model of HIV neurotoxicity. Additionally, ADAM10 is …
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Triazole-linked reduced amide isosteres: An approach for the fragment-based drug discovery of anti-Alzheimer's BACE1 inhibitors and NH-assisted Fürst-Plattner opening of cyclohexene oxides
In the scope of our BACE1 inhibitor project we used an originally designed microtiter plate-based screening to discover 4 triazole-linked reduced amide isosteres that showed modest (single digit micromolar) BACE1 inhibition. Our ligands were designed based on a very potent (single digit nanomolar) …
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Svipgerð stökkbreytingar í APP geninu sem verndar gegn Alzheimer sjúkdómi
… amyloid precursor protein (APP). Ensímin BACE1 og -sekretasi kljúfa APP og við það myndast A. Mikil þörf er á meðferð við AD sem hefur áhrif á sjálfan sjúkdómsganginn en sú meðferð sem er á markaði í dag er eingöngu einkennameðferð. Ný lyf eru í þróun sem hafa bein áhrif myndun A, …
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APP Processing: A Biochemical Competition Influenced by Exercise-Induced Signalling Mediators
… were no statistical differences in ADAM10 and BACE1 mRNA or protein expression with post-exercise serum treatment at either time point. However, there was an increase in the ratio of sAPPα to sAPPβ protein content (p=0.05) after 30 minutes of post-exercise serum treatment. Additionally, 30 …
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Characterization of SERCA function in the hippocampal and prefrontal cortex regions of the brain from C57 and D2 mx mice
… Ca2+ uptake activity assays, western blots, and BACE1 activity assays on homogenates of hippocampus and PFC from C57 and D2 WT and mdx mice. Ca2+ uptake was impaired in mdx mice, more so in the D2 mdx mice, even though SERCA expression was unaltered. Reactive oxygen and nitrogen species (RONS) …
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Determining the mechanism of dichloroacetate-regulated processing of the Alzheimer’s disease-related amyloid precursor protein
… localisation of APP and the activity of BACE1. However, none of these potential mechanisms proved to be involved in the DCA mechanism of action. Therefore, in conclusion, the mechanism(s) behind DCA-mediated changes in APP proteolysis/expression have not yet been identified but could …
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Pathomechanismen der sporadischen Einschlusskörperchenmyositis
… eine zytokinbedingte Hochregulation von BACE1 in vitro belegt werden. Durch siRNA-vermittelten knock down ließ sich die Akkumulation von β-Amyloid im entzündlichen Milieu verhindern. Hierdurch kam es zu einem deutlichen Rückgang von sIBM-relevanten Entzündungs- und Degenerationsmarkern …
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The Processing of Amyloid Precursor Protein in the Central Nervous System of Humans and Rhesus Macaques
… intervention of the β-secretase pathway by a BACE1 inhibitor would affect the α-secretase pathway. Soluble APPβ, sAPPα and Aβ were isolated from rhesus macaque CSF by serial immunoprecipitation. Monkeys were undergoing stable isotope labeling kinetics studies. Isolated APP metabolites …
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Investigating the Role of the Amyloid Precursor Protein in the Pathogenesis of Alzheimer's Disease
… pathway, by increasing levels of the β-secretase BACE1, resulting in increased Aβ production. Finally, we found that dimerization of APP triggered caspase-dependent cleavage of APP and the formation of a second neurotoxic fragment, termed C31, which also mimics the effects of Aβ in hippocampal …
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