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 20 for “"Synucleinopathies"”.
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Modeling disease-related proteins in Saccharomyces cerevisiae : insights into alpha-synuclein and TorsinA biology
… the progression of Parkinson's disease and other synucleinopathies. [alpha]-Syn expression in yeast is associated with many phenotypes that are recapitulated in higher organisms. Here, I used yeast to characterize two naturally occurring splice isoforms of [alpha]-syn, [alpha]-syn[delta]4 and …
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Studies on the Cytoplasmic Inclusions Detected in Parkinson's disease
… as a neuropathological marker in patients with α-Synucleinopathies because it is strongly accumulated with synphilin-1 in the inclusions of their brain cells. They also suggest that LMO7 could be a potential therapeutic target for α-Synucleinopathies.
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Phenotyping Behavioral Disorders in REM Sleep: Study of Digital Biomarkers of Neurodegeneration
… (RBD), a recognized prodromal symptom of alpha-synucleinopathies, among which Parkinson's Disease (PD). By integrating computational approaches with physiological insights, this research presents novel tools and methods for identifying early-stage biomarkers and understanding autonomic …
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Oligomer dynamics for drug discovery against α-synuclein aggregation in Parkinson's disease
… α-synuclein in Parkinson’s disease and related synucleinopathies is a histological hallmark of these conditions, as well as a cytotoxic process with no known disease-modifying interventions. While many studies have sought to develop small molecules or other biologics that may abrogate fibril …
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The prion-like properties of assembled human alpha-synuclein
… well as of rarer diseases, collectively called synucleinopathies. For a long time, it was widely believed that neurodegenerative diseases were cell-autonomous; however, a more recent hypothesis has suggested that some misfolded proteins resemble prions. Thus, aggregated alpha-synuclein shares …
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A deep dive into the liquid droplet state of α-synuclein
… of targeted therapies for PD and related synucleinopathies, addressing a critical need in neurodegenerative disease research.
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Drug discovery for misfolding diseases using structure-based iterative learning
… implicated in Parkinson’s disease and other synucleinopathies, have failed, at least in part due to the challenges in identifying potent compounds in preclinical investigations. In Chapter 2, I describe machine learning approaches to identify small molecule inhibitors of α-synuclein …
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Investigating the Potential Role of α-Synuclein in Tau Aggregation and Toxicity
… Lewy neurites (LNs), are collectively known as synucleinopathies. Even so, tau protein pathology is abundantly found in these diseases. Apart from Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), LBs and LNs have been reported in Alzheimer’s disease …
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Alpha Synuclein Oligomers in Human Pathology: Significance of Nitrative Alpha Synuclein Modifications
… aggregates of αSyn is a pathological hallmark of synucleinopathies such as Parkinson disease (PD) and dementia with Lewy bodies (DLB), which are clinically characterized by motor and cognitive dysfunction. Recent evidence indicates that αSyn oligomer intermediates are the most neurotoxic species. …
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The Influence of Age, Gender, and Thiol Repletion in an In Vivo Model of Lewy Body Disorders
… deficits and are collectively defined as α-synucleinopathies, as they are characterized by hallmark “Lewy bodies” composed of aggregated, fibrillar α-synuclein. It is not certain but often posited that fibrillar α-synuclein seeds the progressive, self-propagating spread of Lewy pathology …
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Parkinson's Disease-Associated Protein VPS13C Regulates Phospho-Rab10-Mediated Lysosomal Function in Human iPSC-Derived Dopaminergic Neurons
… several monogenic and sporadic forms of PD and synucleinopathies (Burbulla et al., 2017; Mazzulli et al., 2011; Nalls et al., 2019). Genetic models of Parkinson’s disease are utilized to initially identify and understand underlying disease mechanisms and to later validate the gained knowledge in …
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Mechanistic modeling of alpha-synuclein aggregation and brain pharmacokinetics for drug development in neurodegeneration
… relevant to Parkinson’s disease (PD) and other synucleinopathies. Building on in vitro aggregation studies and chemical kinetic models, we develop a mechanistic model of aSyn accumulation that incorporates both pure and lipid-mediated aggregation pathways. This unified framework captures key …
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Differential expression of proteins involved in sEV biogenesis and secretion in Parkinson’s disease and Dementia with Lewy bodies
… explores changes in sEV-associated proteins in synucleinopathies, notably Parkinson’s disease (PD) and dementia with Lewy bodies (DLB).<br/><br/>Aims<br/>1. In this study I aim to measure levels of key sEV proteins by focusing on disease-specific brain regions such as the substantia nigra and …
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Development and utilization of Luminex biomarker assays for diagnosis and monitoring of neurodegenerative disease
… implicated in diseases collectively termed α-synucleinopathies. The initial aim of the project was to develop assays for proteins that span a range of neurodegenerative disorders, however, for reasons discussed in the final chapter of this thesis, this was not possible. This project provides …
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Developing an a-synuclein in vitro model for therapeutic testing for Parkinson's disease
… a prominent target for treating PD and related synucleinopathies. Clearing or inhibiting α-synuclein aggregation is one of the main areas of therapeutic research, although it is less clear what therapeutic benefits might be brought by such an approach. In this thesis, I aim to create a more …
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The functional and pathological pathways of α-Synuclein
… the aetiology and pathogenicity of PD and other synucleinopathies.
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Biochemical and Biophysical Studies of the UPR Kinase PERK and its Interactors in Health and Disease
… signalling and eIF2α phosphorylation observed in synucleinopathies and, possibly, other neurodegenerative diseases. To delve deeper into PERK:eIF2α interaction dynamics, FRET biosensors to monitor the interaction between the two proteins in live cells were developed. These successfully reported …
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The spread of pathological assemblies in neurodegenerative disease
… pathogenesis of Parkinson’s disease and other synucleinopathies, and aid the development of novel diagnostic and therapeutic strategies for these debilitating disorders.
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ASSESSMENT OF CELL AND METABOLIC IMPACT OF MICROTUBULE TARGETING AGENTS (MTA) IN NEURODEGENERATION AND NEURON MODELS.
… in the onset and progression of PD and related synucleinopathies, we employed a cell model that naturally showed increased oligomeric pathology due to α-synuclein overexpression, namely SK-N-SH cells, to study the protective impact of Oleuropein aglycone on α-synuclein aggregation and toxicity. …