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 19 of 19 for “"Misfolding Diseases"”.
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Understanding protein misfolding diseases through the development of biophysical methods
… This disease is associated with the aberrant misfolding and aggregation of the Aβ peptide into amyloid plaques in the brains of affected individuals. Despite substantial progress in the understanding of the mechanism of aggregation of Aβ, the variety of ways in which imbalances in brain …
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Drug discovery for misfolding diseases using structure-based iterative learning
… This issue is pressing for neurodegenerative diseases, where the development of disease-modifying drugs has been particularly challenging. The high attrition rate of neurodegenerative drug discovery is especially acute for Parkinson’s disease, where no disease-modifying drugs have yet been …
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Molecular origins of tissue vulnerability to aberrant aggregation in protein misfolding diseases
… we considered another hallmark of these diseases - their characteristic patterns of spreading across the brain - to identify the nature of the transcriptional signature which underlies tissue vulnerability to protein aggregation. By understanding why tissues succumb in their …
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Analysis of the thermodynamic determinants of protein fold specificity in the denatured state ensemble
… drugs to combat the rapidly expanding family of misfolding diseases. Some misfolding diseases are known to be related to non-specific beta sheet formation. The value of this project lies in the detailed analysis between denatured ensemble energetics and sequences, as well as between energetics …
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Mitigating protein aggregation to reduce the toxicity inherent to Parkinson’s and Alzheimer’s diseases
… implicated in the onset and progression of these diseases. In this thesis, I describe our efforts to uncover molecular agents that can reduce the toxicity caused by protein aggregation via targeting the generation, the physiochemical properties or the membrane affinity of oligomeric species. We …
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Fundamental efforts for improving the sensitivity of magnetic resonance force microscopy
… the conformational complexities of protein misfolding diseases and amyloid formation phenomena , caused by complex networks of structural transition reactions linking the monomeric, oligomeric, and polymorphic fibrillar forms of disease-causing proteins, the structures of which have only …
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Nanolithography and nanoscopy methods for the study of biological samples in confined spaces
… group of amyloid pathologies also called protein misfolding diseases. Since the first discovery of amyloid fibrils of the aggregated protein tau in inclusion of Alzheimer brains samples, research has focussed on how amyloids form and their biological relevance in neurodegenerative diseases. …
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Investigating the potential of enhanced neuroprotection through unfolded protein response inhibition and autophagy induction in neurodegeneration
Neurodegenerative diseases pose an immense challenge to the population and health care worldwide. There is a growing need for therapeutic strategies to target these diseases. Many neurodegenerative diseases are classified as protein misfolding diseases (PMDs). Despite their uniqueness, these PMDs …
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Protein and Peptide Solubility - In Silico and In Vitro Approaches
… solubility predictor developed in the Centre for Misfolding Diseases, to assess and improve the solubility of proteins. The goal of this PhD was to develop a new method, built upon the foundations of CamSol, that predicts the solubility of proteins and peptides containing non-natural amino acids …
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Amyloid seeding assays for the selective amplification of tau aggregates from human brain homogenates
… into amyloid inclusions in a diverse class of diseases called tauopathies. A growing body of biochemical and structural literature has now confirmed that tau takes different disease-specific aggregate conformations, which then propagate throughout the brains of afflicted patients. The …
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The eIF2 phosphatase: characterization and modulation
… appearance of certain cellular malfunctions or diseases. However, affecting this balance has been also suggested to have beneficial effects. For example, genetic interference with the PPP1R15A regulatory subunit is proposed to confer protection to mice and cells under ER-stress conditions. This …
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Advances in Microfluidics and DNA Nanotechnology for Biomolecular Analysis
… which are implicated in the pathogenesis of misfolding diseases. In this study, micro-electrophoresis enables the fractionation of heterogeneous protein mixtures in free solution, an operation that is combined with single-molecule microscopy for high-resolution analysis. In a complementary …
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Distant chaperones and N-glycan signals : new mechanisms of secretory pathway proteostasis
… sustained protein production. Unresolved protein misfolding, on the other hand, results in pathological ER stress and tissue dysfunction. Prior work has used small model substrates to show that cells utilize secretory pathway chaperones and tune N-glycosylation to respond to ER stress. This thesis …
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THE LYSOSOMAL AMYLOID AGGREGATION OF B2-MICROGLOBULIN PROMOTES MULTIPLE MYELOMA PROGRESSION: A MOLECULAR FOCUS ON THIS PRO-CANCER MECHANISM
… events that favor the onset of protein misfolding diseases. These conditions are characterized by formation of protein aggregates, which impair tissues and organ functionalities. A widely studied example is β2-microglobulin (β2m), whose aggregation into amyloid fibrils underlies …
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Evaluating suspected CWD feral pig brain samples using RT-QuIC and protocol for the purification and quality control of recombinant monomeric proteins for RT-QuIC assay
… any of a wide</p> <p>range of neurodegenerative diseases that tend to result from an abnormal misfolding and</p> <p>subsequent aggregation of a normal cellular protein. The pathology of each of these diseases</p> <p>is largely dependent upon the nature of the protein aggregate that is responsible …
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Investigating neurodegenerative diseases with small molecule modulators
… underlying cell death in neurodegenerative diseases has proven difficult, due to the complex and interconnected architecture of the nervous system as well as the often pleiotropic nature of these diseases. Cell culture models of neurodegenerative diseases, although seldom recapitulating all …
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Molecular interactions and their impact on life sciences
… with a wide range of neurodegenerative diseases. The three chaperones are crucial components of the cellular proteostasis network and characteristically overexpressed during cell stress. Each chaperone type shows distinct binding behaviour to protein aggregates, which can be related to …
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Microfluidic Approaches for Investigating Aggregated Forms of Disease-Related Proteins
… that lead to disease. There are nearly 50 diseases currently associated with protein misfolding and amyloid formation, among them several neurodegenerative disorders such as Alzheimer's, Parkinson's and prion diseases. Recent evidence indicates that the most toxic species are the low …
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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 …