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 28 for “"misfolded protein"”.
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Disordered Protein Aggregates Are Linked to Changes in the Histone Post-Translational Modification Landscape in Disease and Non-Disease Models
<p>Proper protein folding is a delicate balance that is crucial for normal biological function. In mammals, protein misfolding and aggregation leads to loss of function of the original protein while in many cases being associated with neurodegenerative diseases, eventually leading to death of the …
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Effect of maternal separation on stress-related proteins measured in a 6-hydroxydopamine rat model of Parkinson’s disease
… mitochondrial dysfunction, oxidative stress and misfolded protein aggregation in patients with PD. Since ELS has been shown to negatively affect the nigrostriatal pathway and mitochondrial function, developmental stress may create a vulnerable microenvironment which results in a greater rate of …
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Transgenic complementation of rumpshaker with wild type proteolipid protein
Mutations in the x-linked myelin proteolipid protein 1 gene (PLP1) cause the heterogeneous syndromes of Pelizaeus Merzbacher disease (PMD) and Spastic paraplegia type 2(SPG2) in man (Hudson et al., 2004). A single base change mutation in our spontaneous mouse model rumpshaker (Plpjp-rsh)(Ile186Thr) …
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Characterisation of Truncated Mutant Rhodopsin and its Involvement in the Pathogenesis of Retinitis Pigmentosa
… in the N-terminus of rhodopsin produce severely misfolded protein, which has been shown to cleave at the N-terminus removing the glycosylation sites(Tam & Moritz, 2007),(Krebs, et al., 2010). We aimed to further understand the pathology of retinitis pigmentosa by separating full rhodopsin from …
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Redox Sensing By Yeast Hsp70 Facilitates Modulation of Protein Quality Control and The Cytoprotective Response
… of these aggregates is damage sustained to proteins by oxidative stress. Cellular protein homeostasis (proteostasis) relies on the ubiquitous Hsp70 chaperone family. Hsp70 activity has been previously shown to be modulated by modification of two key cysteines in the ATPase domain by …
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Characterization of the degradation of wild-type and mutant HFE proteins during stress signalling in the endoplasmic reticulum
HFE is a transmembrane protein that becomes N-glycosylated during transport to the cell membrane. It acts to regulate cellular iron uptake by interacting with the Type 1 transferrin receptor and interfering with its ability to bind iron-loaded transferrin. There is also evidence that HFE regulates …
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Frustration of protein folding from in vitro to in vivo
Protein folding, a ubiquitous and vital biological process, where protein random coil transforms into certain conformation in order to fulfill its function. Misfolded protein which fails to acquire proper shape, not only loses its function, but can also cause fatal diseases. In this dissertation, I …
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Mechanisms Behind the Chaperone Activity of Nucleic Acids
… the interplay between nucleic acids and protein aggregation is integral to the understanding of proteostasis, aging, and neurodegenerative disease progression. Nucleic acids are known to modulate the aggregation of PrP, tau, ⍺-synuclein, and other disease relevant proteins. Although the …
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Hierarchical mechanics of functional amyloid protein based materials
Amyloid and amyloid-like proteins are a broad class of misfolded protein structures known for their their roles in a variety of neurodegenerative diseases, but also for their impressive mechanical properties and their propensity to self-assemble at diverse length scales. These properties make …
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Regulation of Protein Degradation at the Endoplasmic Reticulum
… (ERAD) is important for removing damaged or misfolded proteins at the ER membrane, and is central to the physiological regulation of proteins such as HMG-CoA Reductase (HMGCR), the rate limiting enzyme in cholesterol biosynthesis. Under sterol rich conditions, HMGCR is rapidly degraded …
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Mitigating protein aggregation to reduce the toxicity inherent to Parkinson’s and Alzheimer’s diseases
Protein deposition in the form of amyloid fibrils is the hallmark of more than 40 human pathologies, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Misfolded protein oligomers formed as intermediates during the aggregation process have been strongly implicated in the onset and …
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Identification of regulators in autophagosome formation using image-based siRNA screening
… degrade damaged organelles, lipid vesicles and misfolded protein aggregates with implications in various pathological conditions, including neurodegenerative diseases, cancers, and infectious diseases. Autophagy is one of the major intracellular membrane-trafficking processes and its morphology …
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Structure, Mechanism and Chemical Modulation of the Protein Kinase-nuclease Dual-enzyme IRE1
… that derail the proper folding and assembly of proteins in the endoplasmic retriculum (ER) cause misfolded protein accrual in the ER – a toxic condition known as ER stress. The Unfolded Protein Response (UPR) is a signaling system evolved to detect and rectify ER stress. The work I present …
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The Intersection of Neurodegeneration and Mitochondrial Stress in Caenorhabditis Elegans Models of Parkinson's Disease
… hallmarks of PD is the accumulation of the misfolded protein, α-synuclein (α-syn). Emerging evidence suggests an interplay between α-syn and mitochondria leads to a disruption of mitochondrial function, impaired energy production, and increased oxidative stress. During stress, the …
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Function and Properties of groE Chaperonins in Bacterial and Mammalian Cells
… most polypeptides <em>in vivo</em>, and protect proteins against aggregation when a cell is under stress. The GroESL proteins of <em>Escherichia coli</em> are the best characterized of the ringed chaperones, or chaperonins. Chaperonins of the eukaryotic cytoplasm interact with a limited number of …
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The Genetic Basis Of Neurodegenerative Diseases: The Role Of Sel1L In Tau Pathology And Neuropathology
… to encode an endoplasmic reticulum (ER) membrane protein and is highly expressed in CNS neurons. To investigate the potential association between neurodegeneration and dysfunction of SEL1L, we generated and characterized mice with a neuron-specific knockout of SEL1L (Sel1l-NKO). Sel1l-NKO mice …
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Protein quality control in the mammalian endoplasmic reticulum
Quality control is an important part of protein biogenesis. Aberrant proteins must be destroyed before they aggregate and cause deleterious effects. Failure to do so can result in cell death or malfunction and, ultimately, disease. Quality control involves the recognition of misfolded proteins and …
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The Molecular Interaction Between Type Ii Diabetes and Alzheimer’S Disease Through Cross-Seeding of Protein Misfolding
… other complications. T2D and AD are considered protein misfolding disorders (PMDs). PMDs are characterized by the presence of misfolded protein aggregates, such as in T2D pancreas (islet amyloid polypeptide - IAPP) and in AD brain (amyloid– Aβ) of affected individuals. The misfolding and …
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Probabilistic Reconstruction and Comparative Systems Biology of Microbial Metabolism
… addresses the question of why highly expressed proteins evolve slowly, showing that, at least for Escherichia coli, this is more likely to be a consequence of selection for translational efficiency than selection to avoid misfolded protein toxicity. The second project investigates genetic …
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Proteomics studies of protein homeostasis and aggregation in ageing and neurodegeneration
Upon ageing, a progressive disruption of protein homeostasis often leads to extensive protein aggregation and neurodegeneration. It is therefore important to study at the proteome level the origins and consequences of such disruption, which so far have remained elusive. Addressing this problem has …
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