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 13 of 13 for “"Proteotoxicity"”.
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Quantitative analysis of proteotoxicity associated with neurodegenerative disease
… part of this thesis, I combined modeling of the proteotoxicity of polyglutamine (as exemplified in Huntington's Disease) in Saccharomyces cerevisiae with microfluidics and automated microscopy. From these studies, I have found that glutamine-rich proteins suppress the toxicity of poly-glutamine …
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Vitamin B12 impacts amyloid-β induced proteotoxicity by regulating the methionine/s-adenosylmethionine cycle
… elegans to define the impact of diet on Aβ proteotoxicity. Caenorhabditis elegans are free-living, non-parasitic nematodes that can be maintained in laboratory settings with E. coli OP50 or E. coli HB101 used for food. I discovered nematodes raised on HB101 experienced a delay in Aβ-induced …
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Severely Stressed Astrocytes Adapt to Injury and Still Protect Neighboring Neurons
… characterized by protein-misfolding stress, or proteotoxicity, in both neurons and glia. However, the impact of proteotoxicity on glia is less well understood than in neurons. Astrocytes are an abundant type of glia and play an essential role in brain homeostasis by supporting neuronal …
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Topographical Differences in Stress Vulnerability in Experimental Parkinson's Disease
… spread of protein misfolding stress, or proteotoxicity, across the brain. During this protracted process, the allocortex of the temporal lobe develops protein inclusions before the neocortex in the frontal and parietal lobes. In the present study we tested the hypothesis that the staged …
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Global and chromosome-specific consequences of aneuploidy in Saccharomyces cerevisiae
… an array of known cellular phenotypes including proteotoxicity, genomic instability and slowed proliferation. Organisms with constitutional genomic imbalance are less fit than their euploid counterparts, and aneuploidy is the leading cause of spontaneous abortion in humans. Although much has been …
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Nutlin-3 sensitizes cancer cells to bortezomib via induction of paraptosis-associated cell death
… of the misfolded proteins and subsequent proteotoxicity in tumor cells, the proteasome is considered a target for cancer therapies. Bortezomib, the first FAD approved proteasome inhibitor, is now in the clinic to effectively treat multiple myeloma and mantle cell lymphoma, but its efficacy …
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The Discovery of p62-dependent Processing Bodies
… NDDs, provides a novel mechanism of proteotoxicity-induced neuroinflammation in <br/>NDDs. Previously, p62 had been reported to negatively regulate the NLRP3 inflammasome <br/>and therefore, this study has suggested a novel role of p62 in the positive regulation of the <br/>NLRP3 …
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The Influence of Age, Gender, and Thiol Repletion in an In Vivo Model of Lewy Body Disorders
… protected primary neuron cultures against proteotoxicity, including that of α-synuclein fibrils, and the mechanism appeared to be partly dependent on the chaperone activity of heat shock protein 70. These findings were expanded to an in vivo study, in which mice were fed N-acetyl cysteine …
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Quality control of protein complex assembly
… is common. Acute aneuploidy is known to cause proteotoxicity, probably as a consequence of high orphan burden. How orphan subunits are targeted for degradation to maintain protein homeostasis remains an unanswered question for most of the cell’s major protein complexes. The work described in …
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Using yeast to study neurodegenerative diseases : amyloid formation as a protective mechanism and a new Alzheimer's disease model
… investigate how amyloid formation contributes to proteotoxicity. Ectopic overexpression of Rnq1 was extremely toxic, but only if the endogenous Rnq1 protein had adopted its amyloid conformation. The Hsp40 co-chaperone Sis1 was able to counteract the Rnq1-induced toxicity when co-overexpressed. In …
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Regulation of transcription factors NRF2 and HSF1 in mediating cellular stress responses
… of a battery of genes involved in ameliorating proteotoxicity. Several small molecule activators of the KEAP1/NRF2/ARE pathway have been shown to activate HSR through the activation of HSF1. Work in this thesis focused on one such dual activator, the dietary agent phenethyl isothiocyanate …
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Carnosine’s inhibitory effect on glioblastoma cell growth is independent of its cleavage
… supports mitochondrial activity and diminishes proteotoxicity. Current studies mainly consider these benefits in muscle tissue and refer to cardiovascular and neurodegenerative diseases. In 1986, Nagai and Suda first revealed tumor growth inhibition after using carnosine in a sarcoma mouse …
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Mechanisms Underlying The Heterogeneous Sensitivities of Cancer Cells to Proteasome Inhibitors
<p>The mechanisms underlying cellular response to proteasome inhibitors have not been clearly elucidated in solid tumor models. Evidence suggests that the ability of a cell to manage the amount of proteotoxic stress following proteasome inhibition dictates survival. In this study using the …