Дисертації з теми "Protein misfolding and aggregation"
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BROGGINI, LUCA. "MOLECULAR DETERMINANTS UNDERLYING PROTEIN MISFOLDING AND AGGREGATION." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/831967.
Повний текст джерелаBuell, Alexander Kai. "On the kinetics of protein misfolding and aggregation." Thesis, University of Cambridge, 2011. https://www.repository.cam.ac.uk/handle/1810/270324.
Повний текст джерелаTodorova, Nevena, and Nevena Todorova@rmit edu au. "Molecular modelling of peptide folding, misfolding and aggregation phenomena." RMIT University. Applied Science, 2009. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20091130.111240.
Повний текст джерелаDevlin, Glyn L. "The mechanisms of serpin misfolding and its inhibition." Monash University, Dept. of Biochemistry and Molecular Biology, 2003. http://arrow.monash.edu.au/hdl/1959.1/9469.
Повний текст джерелаBorgia, Madeleine Bridget Windsor. "Studies of the aggregation and misfolding of titin Ig-like domains." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609256.
Повний текст джерелаFreer, Rosie. "Molecular origins of tissue vulnerability to aberrant aggregation in protein misfolding diseases." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/275420.
Повний текст джерелаXu, Mingming. "Discovery of inhibitors against a-synuclein aggregation." Thesis, Griffith University, 2020. http://hdl.handle.net/10072/392373.
Повний текст джерелаThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
Full Text
Belfiore, Ramona. "Protein Misfolding and Aggregation in Neurodegeneration: In Vitro And In Vivo Study Cases." Doctoral thesis, Università di Catania, 2018. http://hdl.handle.net/10761/4178.
Повний текст джерелаBinger, Katrina Jean. "The reversibility of amyloid fibril formation." Connect to thesis, 2009. http://repository.unimelb.edu.au/10187/4912.
Повний текст джерелаThe initial stages of the project were to develop a model for apoC-II amyloid fibril formation. This was achieved by analysis of the concentration dependent kinetics of apoC-II amyloid fibril formation, and correlation of these data with the final size distribution of the fibrils, determined by sedimentation velocity experiments. On the basis of these studies, a new reversible model for apoC-II amyloid fibril formation is proposed that includes fibril breaking and re-joining as integral parts of the assembly mechanism. The model was tested by rigorous experimentation, with antibody-labelling transmission electron microscopy providing direct evidence for spontaneous fibril breaking and re-joining.
The development of this model for apoC-II fibril assembly provided the foundation for experiments to investigate factors that promote, inhibit or reverse amyloid fibril formation. Factors that were considered include a molecular chaperone protein, αB-crystallin, and a chemical modification, methionine oxidation. Investigations on the effect of αB-crystallin revealed that the inhibition of apoC-II fibril formation occurs by two distinct mechanisms: transient interaction with monomer preventing oligomerisation, and binding to mature fibrils, which inhibits fibril elongation. Studies on the effect of methionine oxidation on apoC-II fibril formation showed that both the assembly and stability of the fibrils was affected by this modification. ApoC-II contains two methionine residues (Met-9 and Met-60), and upon oxidation of these residues fibril formation was inhibited. In addition, the treatment of pre-formed fibrils with hydrogen peroxide caused dissociation of the fibrils via the oxidation of Met-60, located with the fibril core structural region. The final chapter details the development of antibodies that specifically recognise the conformation of apoC-II amyloid fibrils, which provide the foundation for future studies to examine the role that apoC-II amyloid fibrils play in disease.
Overall, this thesis reveals the dynamic and reversible nature of amyloid fibril formation. New insight is also obtained of the general stability of amyloid fibrils and the processes that may regulate their formation, persistence and disease pathogenesis in vivo.
Daidone, Isabella. "Folding, misfolding and aggregation of proteins and peptides: a molecular dynamics study." Doctoral thesis, La Sapienza, 2005. http://hdl.handle.net/11573/917339.
Повний текст джерелаFlagmeier, Patrick. "An interdisciplinary approach to studying mechanistic, structural and toxic features of protein aggregates associated with neurodegenerative disorders." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/274344.
Повний текст джерелаWiberg, Henning. "Analytical Approaches to Neurodegenerative Disease Protein Aggregation." Licentiate thesis, KTH, Analytisk kemi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-34027.
Повний текст джерелаLapinska, Urszula. "Microfluidics and chemical kinetics to analyse protein interactions, aggregation, and physicochemical properties." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/284929.
Повний текст джерелаCHOUDHARY, DHAWAL. "Studio a livello di singola molecola del folding, misfolding e aggregazione di proteine e dell’attività chaperonica della HSPB8." Doctoral thesis, Università degli studi di Modena e Reggio Emilia, 2020. http://hdl.handle.net/11380/1199862.
Повний текст джерелаOptical tweezers have evolved as an exemplary Single Molecule Force Spectroscopy (SMFS) technique over the past three decades. A distinct and bio medically relevant application of Optical Tweezers is their ability to observe directly at single molecule level the folding, misfolding and aggregation of protein molecules. Additionally the dynamic approach of Optical Tweezer setup also allows for the isolated study of interactions between two or more biomolecules, such as chaperone-protein interactions, in real time. The medical relevance of such studies stems from the fact that misfolding and aggregation of proteins are deleterious processes and have been linked to many neurodegenerative disorders. While molecular chaperones have evolved as an evolutionarily conserved sword and shield mechanism against such deleterious processes, wherein their holdase action acts as a shield preventing further aggregation of misfolded protein species and their foldase action acts as a sword and actively assists misfolded structure to regains their natively folded state. The dysfunction of this chaperone activity is also cytotoxic and can lead to loss of proteostasis. The present thesis dwells deeper in this specific application of Optical tweezer. The thesis will elaborate upon how optical tweezers can extract the mechanistic details of the folding and misfolding of protein molecules by reviewing the experiments performed on NCS-1 (Neuronal Calcium Sensor 1). It will also discuss the experimental approach taken by SMFS techniques like Optical Tweezers and AFM (Atomic Force Microscopy) to study the structural and functional dynamics of molecular chaperones. Furthermore, the thesis will explore the recent developments in Optical Tweezers and their biological applications. Finally, I describe the results of experiments we have carried out on the maltose binding protein to elucidate the mechanism of action of the chaperone HSPB8. We have mechanically denatured homotetramers of MBP as well as single MBP molecules and analyzed their folding and aggregation processes in the presence and absence of wild-type HSPB8 and its mutant form HSPB8-K141E/N. Our results reveal a strong holdase activity of wild type HSPB8, which either prevents completely the aggregation of denatured MBP molecules or allows the substrate to form only small and mechanically weak aggregates while this holdase activity is significantly suppressed in the mutant. Moreover, and importantly, a careful analysis of the data also discloses an unexpected foldase activity of both wild type and mutated forms of HSPB8, which guides the folding process of denatured MBP molecules into their native states. Our findings highlight new mechanisms of interaction between HSPB8 and its substrates and suggest a more complex physiological role for this chaperone than previously assumed.
Villar, i. Piqué Anna. "Characterization of intracellular protein aggregates." Doctoral thesis, Universitat Autònoma de Barcelona, 2013. http://hdl.handle.net/10803/120241.
Повний текст джерелаDuring the last decades, protein aggregation has become a dynamic research topic extending across distinct investigation fields, including biochemistry, biotechnology, biomedicine and nanotechnology. On one side, the accumulation of proteins into insoluble amyloid deposits constitutes a common hallmark of many human disorders, known as conformational diseases. On the other side, from a biotechnological point of view, protein deposition is regarded as a usual hindrance in the production of recombinant proteins, which generally assemble into intracellular inclusion bodies. Although inclusion bodies were traditionally considered unstructured particles lacking of interest, the increasing number of evidences indicating that these aggregates contain amyloid-like structure pave the way for employing them in the study of amyloid deposition. The thesis presented here recapitulates the work belonging to a set of publications concerning amyloid protein aggregation in the intracellular space. In three of these works, we use three distinct cellular models phylogenetically distant (bacteria, yeast and plants) to address the formation of protein deposits with the aim to characterize them and to analyze their impact in the cellular metabolism. In a complementary publication, we exploit bacterial aggregates to develop an in vitro screening assay for amyloid modulators. Finally, we also include two revision works about protein deposition in bacteria and its role as model in the study of amyloid aggregation. The data collected from these studies indicate that aggregation into amyloid structures is a general property of polypeptides and a ubiquitous phenomenon in Nature. However, the apparition of these deposits in the cellular environment can be accompanied by a certain degree of toxicity. Here, we analyze the aging effect promoted by intracellular inclusion bodies in bacterial cells. In addition, we report how both prokaryotic and eukaryotic cells are endowed with a powerful protein quality machinery to challenge this damaging scenario. Moreover, the deep characterization of bacterial protein aggregates and their formation process permits their use as a tool in the searching for amyloid aggregation inhibitors with putative biomedical and pharmaceutical interest. Overall, this thesis delves into the study of amyloid protein aggregation and adds insights to employ simple organisms as relevant cellular models.
Gragg, Megan Ellen. "Mutant Rhodopsins in Autosomal Dominant Retinitis Pigmentosa Display Variable Aggregation Properties." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1522935340252319.
Повний текст джерелаVecchi, Giulia. "Proteomics studies of protein homeostasis and aggregation in ageing and neurodegeneration." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/273348.
Повний текст джерелаRoostaee, Alireza. "Importance of dimerization in aggregation and neurotoxicity of Prion and [alpha]-Synuclein in prion and Parkinson's diseases." Thèse, Université de Sherbrooke, 2012. http://hdl.handle.net/11143/6650.
Повний текст джерелаSalazar, Vázquez Lilian Shadai. "How protein misfolding can lead to cellular dysfunction and disease : the case of islet amyloid polypeptide involved in type 2 diabetes mellitus." Thesis, Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2019SORUS371.pdf.
Повний текст джерелаTo have a biological function, a protein folds into a specific structure. The cell controls the correct folding of the proteins and has mechanisms to detect and eliminate misfolded proteins; nevertheless some proteins achieve to avoid this control process. Amyloid proteins are misfolded proteins that form a characteristic type of elongated amyloid fibril; depending on the protein sequence and the site of amyloid deposition they are related to different human diseases. Islet amyloid polypeptide (IAPP) a 37 amino acid peptide co-produced and co-secreted with insulin by β-cells, is involve in type 2 diabetes disease and belongs to this group of amyloid proteins. The fibrils are formed in the pancreatic islet. However the conditions under which the fibers are formed and their cytotoxicity in other cells are still unknown. Here we show that the human IAPP flanking peptides, produced during hIAPP maturation, N-terminal and C-terminal are not amyloidogenic and the toxicity of human IAPP in different cell lines. We find through biophysical assays ThT, TEM and CD that N-terminal and C-terminal residues of IAPP do not form fibrils in solution, in artificial vesicles or in cells and do not modify hIAPP toxic effect. For the toxicity of hIAPP we use Ins-1 (β-cells), SHSY5 (neuronal), F442A and 3T3L1 (adipose), mhAT3F (hepatic) and C2C12 (muscle) lines. We observe fibril formation in all cell lines, however the toxicity do not related directly with the presence of fibril. We anticipate our assay to be a starting point for more in vitro studies in different cells lines. Furthermore, IAPP fibril inhibition could be a target for anti-amyloid drug development
Robinson, Philip John. "The folding, misfolding and aggregation of prions." Thesis, University of Warwick, 2009. http://wrap.warwick.ac.uk/2792/.
Повний текст джерелаSubramaniam, Vinod. "Biophysics of protein misfolding." Enschede : University of Twente [Host], 2007. http://doc.utwente.nl/58042.
Повний текст джерелаAlmstedt, Karin. "Protein Misfolding in Human Diseases." Doctoral thesis, Linköpings universitet, Biokemi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-21077.
Повний текст джерелаLi, W. "Investigation and manipulation of SOD1 mutant misfolding, aggregation and seeding." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1558299/.
Повний текст джерелаSchmittschmitt, Jason Peter. "Biophysical characterization of protein folding and misfolding." Texas A&M University, 2003. http://hdl.handle.net/1969.1/46.
Повний текст джерелаGuest, William Clay. "Template-directed protein misfolding in neurodegenerative disease." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/41990.
Повний текст джерелаSuk, Ji Young. "Molecular consequences of protein misfolding mutations in FBN1." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270282.
Повний текст джерелаRoboti, Peristera. "Disease-related misfolding of the myelin proteolipid protein." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.493943.
Повний текст джерелаNerelius, Charlotte. "Protein misfolding and amyloid formation : strategies for prevention /." Uppsala : Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, 2009. http://epsilon.slu.se/200941.pdf.
Повний текст джерелаLocker, C. Rebecca. "Minimalist models of proteins : misfolding and folding affinity." Diss., Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/27573.
Повний текст джерелаPokrishevsky, Edward. "Induction of wild-type SOD1 misfolding, aggregation and its cell-to-cell propagation." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/61079.
Повний текст джерелаMedicine, Faculty of
Experimental Medicine, Division of
Medicine, Department of
Graduate
Lane, Fiona Mary. "Defining mechanisms of neurodegeneration associated with protein misfolding diseases." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/19542.
Повний текст джерелаLang, Lisa. "SOD1 Aggregation : Relevance of thermodynamic stability." Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-139943.
Повний текст джерелаLeinartaité, Lina. "Zinc in folding and misfolding of SOD1 : Implications for ALS." Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-107543.
Повний текст джерелаAt the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.
Scheinost, Johanna C. "A cholesterol oxidative metabolite and its role in protein misfolding." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504523.
Повний текст джерелаGriffiths-Jones, Samuel R. "Peptide models for protein beta-sheets." Thesis, University of Nottingham, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364650.
Повний текст джерелаMünch, Christian. "Initiation and propagation of mutant superoxide dismutase 1 misfolding." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609791.
Повний текст джерелаNuhu, Mariam. "Protein-protein interactions and aggregation in biotherapeutics." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/proteinprotein-interactions-and-aggregation-in-biotherapeutics(1dba3d89-1474-486c-9eb9-6e21b4616dd9).html.
Повний текст джерелаOuteiro, Tiago Fleming de Oliveira. "Yeast as a model organism to study diseases of protein misfolding." Doctoral thesis, Universidade do Porto. Reitoria, 2004. http://hdl.handle.net/10216/10638.
Повний текст джерелаO'Connor, Matthew. "Ruminant prion disease detection and characterisation using protein misfolding cyclic amplification." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/41599/.
Повний текст джерелаOuteiro, Tiago Fleming de Oliveira. "Yeast as a model organism to study diseases of protein misfolding." Tese, Universidade do Porto. Reitoria, 2004. http://hdl.handle.net/10216/10638.
Повний текст джерелаKemplen, Katherine Rosemary. "Biophysical studies of folding and misfolding in tandem repeat proteins." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709235.
Повний текст джерелаGurry, Thomas. "Order, disorder, and protein aggregation." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/97347.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references (pages 114-124).
Protein aggregation underlies a number of human diseases. Most notably, it occurs widely in neurodegenerative diseases, including Alzheimer's and Parkinson's. At the molecular level, neurotoxicity is thought to originate from toxic gains of function in multimeric aggregates of proteins that are otherwise predominantly monomeric and disordered, fluctuating between a very large number of structurally dissimilar states on nano- and microsecond timescales. These proteins, termed Intrinsically Disordered Proteins (IDPs), are notoriously difficult to probe using traditional biophysical techniques. In order to obtain structural information pertaining to the aggregation of IDPs, it is often necessary to develop computational and modeling tools, both to leverage the full extent of the experimental data, and to generate testable predictions for future experiments. In this thesis, I present three separate computational studies studying the formation of multimeric aggregates in IDPs, spanning different aspects of the aggregation process, from early nucleation events to fibril elongation. In the first study, I present a conformational ensemble of a-synuclein, the culprit protein of Parkinson's disease, constructed using a Variational Bayesian Weighting algorithm in combination with NMR data collected by our collaborators. We find that the data fit a description in which the protein predominantly exists as a disordered monomer but contains small quantities of multimeric states containing both helical and strand-rich conformations. In the second study, I focus on the process of amyloid fibril elongation in the Amyloid-[beta] (A[beta]) peptide of Alzheimer's disease. I compute the free energy surface associated with the fibril elongation reaction, and find that elongation of both A[beta]40 and A[beta]42 experimental fibril structures occurs on a downhill free energy pathway, proceeding via an obligate, fibril-associated hairpin intermediate. The fibril-associated hairpin is significantly more stable (relative to the fibrillar, elongated state) in A[beta]42 compared with A[beta]40, suggesting a potential clinical target of interest. Finally, I present lengthy, all-atom molecular simulations that suggest that nucleation of the minimum aggregating fragment of c-synuclein proceeds via a helical intermediate, requiring a structural conversion into a strand-rich nucleating species via a stochastic process of individual helices unfolding and self-associating via backbone hydrogen bonds.
by Thomas Gurry.
Ph. D.
Knowles, Tuomas Pertti Jonathan. "Physical aspects in protein aggregation." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612258.
Повний текст джерелаWhite, Duncan Alexander. "Biophysical features of protein aggregation." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609696.
Повний текст джерелаLast, Alexander M. "Intermediates in protein folding and misfolding revealed by electrospray ionisation mass spectrometry." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393383.
Повний текст джерелаLemin, Andrew James. "The unfolded protein response and HLA-B27 misfolding : implications for ankylosing spondylitis." Thesis, Durham University, 2010. http://etheses.dur.ac.uk/797/.
Повний текст джерелаBastidas, Oscar. "Computational Study of Protein-Protein Interactions in Misfolded States." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3521.
Повний текст джерелаBarber, Michael. "Mechanisms and prevention of protein aggregation." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:924a4f23-a2d3-49af-b201-f29295bdf442.
Повний текст джерелаWain, Rachel. "Studies of protein folding and aggregation." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270186.
Повний текст джерелаWilkins, Deborah K. "Studies of protein denaturation and aggregation." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325146.
Повний текст джерела