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 106 for “"Protein aggregates"”.
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Single-molecule techniques for mapping protein aggregates
Proteins in our body are usually folded to carry out their physiological functions. However, they can become misfolded and aggregated throughout the lifetime of a cell. These proteins can be degraded or cytotoxic, the latter of which leads to diseases such as neurodegeneration and cancers. …
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PNA-protein conjugates for nano-scale modeling of protein aggregates
Abstract Programmable assembly of proteins on molecular frameworks requires the development of facile and orthogonal chemical approaches and molecular scaffolds. In this research, the unique characteristics of PNA were applied to create controllable protein assemblies directed by precise PNA-DNA …
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Characterisation of neurodegenerative diseases derived protein aggregates using improved single-molecule pull-down
… have revealed the pathogenic significance of protein aggregates in ND, this PhD thesis aims to answer 2 key questions in the field: How to characterise these protein species in the complex human samples and How to find the key species associated with these diseases. To address these questions, …
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Structure determination of proteins and protein aggregates by magic-angle spinning solid-state NMR
… determination technique uniquely suited to study protein aggregates and fibrils. Unlike solution NMR or X-ray crystallography, SSNMR can obtain atomic resolution structural information on samples of protein fibrils which are insoluble and do not produce X-ray diffracting crystals. As SSNMR begins …
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Biophysical methods to study the ubiquitination of amyloidogenic proteins and proteasomal responses to protein aggregates
The accumulation of misfolded proteins is a universal mechanism in neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD) and prion disease. In mammalian cells, the majority of misfolded proteins are degraded by the ubiquitin-proteasome system (UPS), in which …
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An interdisciplinary approach to studying mechanistic, structural and toxic features of protein aggregates associated with neurodegenerative disorders.
The misfolding and aggregation of proteins is closely associated with more than fifty human disorders, including Alzheimer's and Parkinson's diseases, all of which are currently incurable and many represent a major threat to human life. The mechanism of protein aggregation is subject to extensive …
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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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The Systems Biology of the Protein Quality Control
… protease, is the main powerhouse for protein degradation in all eukaryotic cells. Proteostasis is maintained by the ubiquitin-proteasome system (UPS) targeting aberrant proteins whose accumulation and aggregation are hallmarks of aging and neurodegenerative disorders. Previous studies …
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Aggregation of IgG mAb Biotherapeutics: Sources, Methods of Characterization, and Biological Implications
One of the predominant concerns with protein therapeutics is their tendency to aggregate at various stages of protein production, purification, filling, transportation, and administration. This occurrence has biological significance; while there is no definite, general cause and effect relationship …
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Investigating the protein disaggregation machinery in the early secretory pathway
Protein misfolding and subsequent aggregation represent key pathological features in various forms of dementia, notably Alzheimer’s disease (AD). AD is characterised by the presence of extracellular plaques, comprised of aggregated amyloid beta (Aβ) peptides, and intracellular neurofibrillary …
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The Development and Application of Ultra-sensitive Protein Aggregate Detection Techniques
… of ultra-sensitive techniques for detecting protein aggregates. It begins by studying the role of apolipoprotein E (apoE) in amyloid- β (Aβ) pathology in Alzheimer’s disease (AD). The isoform-specific and lipidation-specific behaviours of apoE and the co-aggregates formed with A β are …
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Regulation of mTORC1 by homocysteine and its effects on autophagy in human and mouse neuronal tissues
… Homocysteine is sensed by a constitutive protein complex composed of leucyl-tRNA-synthetase (LeuRS) and folliculin (Flcn), which regulates mTOR tethering to lysosomal membranes. In hyper-homocysteinemic human cells and cystathionine [beta]-synthase-deficient mouse brains, an acute and …
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Biological Consequences of Polyglutamine Repeats in Drosophila Muscle
… encoding a glutamine tract in the affected protein. Accumulation of these mutant polyQ proteins leads to formation of insoluble protein aggregates that impair many vital cellular processes. This manifests in neurodegenerative symptoms like progressive loss of motor control, cognitive …
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Fluorescence correlation spectroscopy: ultrasensitive detection in clear and turbid media
… concentrations of cells, bacteria, viruses, and protein aggregates in turbid fluids for clinical and biotechnological applications. The anticipated applications of this technique are many. They range from the determination of the somatic cell count in milk for the dairy industry, to the …
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Development of Novel Molecular Imaging Contrast Agents for Detection of Oxidative Stress
… interaction between oxidative stress and protein aggregates. To scrutinise this relationship, both bulk and single-molecule fluorescence imaging methods were used to assess the capability of novel bifunctional fluorescence dyes to localise the presence of the two putative disease-causing …
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Cardiomyocyte Autophagy Is Induced by Protein Aggregation in Heart Disease
… generation of reactive oxygen species, protein damage, and protein aggregation in the acute period of pressure overload. Given the simultaneous presence of autophagosomes and aggregates, and autophagy's role in bulk degradation, I postulated these events were mechanistically linked. I …
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Pathogenesis of Neurodegenerative Diseases via Templated Recruitment
… diseases is the deposition of filamentous protein aggregates in the central nervous system (CNS), including neurofibrillary tangles (NFTs) composed of tau, and Lewy bodies (LBs) consisting of α-synuclein (α-syn), which are the hallmark lesions of Alzheimer's disease (AD) and Parkinson's …
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Single-molecule studies of alpha-synuclein and abeta in Parkinson’s disease derived biofluids
… disorders is deposits of fibrillar protein aggregates in the human brain. However, recent evidence suggests that the small soluble aggregates of alpha-synuclein (αS) and Abeta (Aβ), often referred to as oligomers, are more neurotoxic than mature fibrils. Thus, this work aims to study …
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RNA-binding Proteins and RNA-DNA Hybrids Regulate Repetitive DNA Stability in Health and Disease
… integrity of repetitive loci. The RNA-binding protein Ataxin-2 (Pbp1 in yeast) regulates the stability of rDNA and yeast Ty1 retrotransposons. Interestingly, the human protein (ATXN2) undergoes trinucleotide repeat expansion in the neurodegenerative diseases spinocerebellar ataxia type II …
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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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