Global ETD Search

241	Multi-scale Molecular Dynamics Simulations of Membrane-associated Peptides Zhao, Jun January 2013 (has links) No description available. Biogeochemistry Bioinformatics Biophysics Biostatistics Chemical Engineering Computer Engineering Engineering Molecular Physics Pharmaceuticals Physical Chemistry Physics Quantum Physics molecular dynamics Monte Carlo simulation potential mean force amyloid oligomers antimicrobial peptides self assembled monolayer type 2 diabetes alzheimer disease ion channel hemolysis amylin membrane associated peptides
242	Etude de l'implication des cellules microgliales et de l'α-synucleine dans la maladie neurodégénérative de Parkinson / Microglia and α-synuclein implication in Parkinson's disease Moussaud, Simon 25 February 2011 (has links) Les maladies neurodégénératives liées à l’âge, telle celle de Parkinson, sont un problème majeur de santé publique. Cependant, la maladie de Parkinson reste incurable et les traitements sont très limités. En effet, les causes de la maladie restent encore mal comprises et la recherche se concentre sur ses mécanismes moléculaires. Dans cette étude, nous nous sommes intéressés à deux phénomènes anormaux se produisant dans la maladie de Parkinson : l’agrégation de l’α-synucléine et l’activation des cellules microgliales. Pour étudier la polymérisation de l’α-synucléine, nous avons établi de nouvelles méthodes permettant la production in vitro de différents types d’oligomères d’α-synucléine. Grâce à des méthodes biophysiques de pointe, nous avons caractérisé ces différents oligomères à l’échelle moléculaire. Puis nous avons étudié leurs effets toxiques sur les neurones. Ensuite, nous nous sommes intéressés à l’activation des microglies et en particulier à leurs canaux potassiques et aux changements liés au vieillissement. Nous avons identifié les canaux Kv1.3 et Kir2.1 et montré qu’ils étaient impliqués dans l’activation des microglies. En parallèle, nous avons établi une méthode originale qui permet l’isolation et la culture de microglies primaires issues de cerveaux adultes. En comparaison à celles de nouveaux-nés, les microglies adultes montrent des différences subtiles mais cruciales qui soutiennent l’hypothèse de changements liés au vieillissement. Globalement, nos résultats suggèrent qu’il est possible de développer de nouvelles approches thérapeutiques contre la maladie de Parkinson en modulant l’action des microglies ou en bloquant l’oligomérisation de l’ α-synucléine. / Age-related neurodegenerative disorders like Parkinson’s disease take an enormous toll on individuals and on society. Despite extensive efforts, Parkinson’s disease remains incurable and only very limited treatments exist. Indeed, Parkinson’s pathogenesis is still not clear and research on its molecular mechanisms is ongoing. In this study, we focused our interest on two abnormal events occurring in Parkinson’s patients, namely α-synuclein aggregation and microglial activation. We first investigated α-synuclein and its abnormal polymerisation. For this purpose, we developed novel methods, which allowed the in vitro production of different types of α-synuclein oligomers. Using highly sensitive biophysical methods, we characterised these different oligomers at a single-particle level. Then, we tested their biological effects on neurons. Afterwards, we studied microglial activation. We concentrated our efforts on two axes, namely age-related changes in microglial function and K+ channels in microglia. We showed that Kv1.3 and Kir2.1 K+ channels are involved in microglial activation. In parallel, we developed a new approach, which allows the effective isolation and culture of primary microglia from adult mouse brains. Adult primary microglia presented subtle but crucial differences in comparison to microglia from neo-natal mice, confirming the hypothesis of age-related changes of microglia. Taken together, our results support the hypotheses that microglial modulation or inhibition of α-synuclein oligomerisation are possible therapeutic strategies against Parkinson's disease. Vieillissement Maladies neurodégénératives Maladie de Parkinson Neurodégénération Α-synucléine Oligomères Toxicité Dopamine Neurones Neuroinflammation Microglies Immunité du cerveau Lignée cellulaire C8-B4 Cultures primaires Méthode d’isolation in vitro Patch-clamp Electrophysiologie Canaux potassiques Kv1.3 - Kir2.1 Oxyde nitrique Cytokines Aging Neurodegenerative disorders Parkinson’s disease Neurodegeneration Α-synuclein Oligomers Toxicity Dopamine Neurons Neuroinflammation Microglia Brain macrophages Brain immunity C8-B4 cell line Primary culture In vitro isolation method Patch-clamp Electrophysiology Potassium channels Kv1.3 - Kir2.1 Nitric oxide Cytokines 612 616.9
243	Bovint serum albumin påverkar överlevnad och Aβ-nivåer i Alzheimers sjuka Drosophila flugor. : Bovine serum albumin affects survival and Aβ-levels in Alzheimer's diseased Drosophila flies. Tani, Milena January 2024 (has links) Alzheimer's disease (AD) was first described more than 100 years ago and is today the most common cause of dementia. It is one of the progressive neurodegenerative diseases that affect 47 million people around the world between the ages of 60 and 90. One of the contributing factors to AD is extracellular amyloid – β (Aβ) plaques that form as a result of protein aggregation. These Aβ proteins are neurotoxic, leading to degeneration of brain neurons and loss of cognitive abilities. Because AD largely affects society, researchers are constantly working to find a cure, which currently does not exist. The purpose of this study was to use Drosophila melanogaster as a living organism model for the expression of two types of Aβ proteins related to AD, Arctic (Glu22Gly) and TandemAβ, and to study the survival of these AD flies when Bovine serum albumin (BSA) was added to the fly food. The hypothesis was that BSA would be effective in slowing down and/or preventing formation of toxic Aβ-aggregates. The focus was therefore to investigate whether the AD flies would live longer if they were allowed to eat Bovine serum albumin and whether the soluble/insoluble Aβ levels in these flies would decrease in comparison to the control AD flies that were not allowed to eat BSA. The effect of BSA on toxicity was evaluated using survival assay on male flies and the levels of soluble/insoluble Aβ were evaluated using Meso Scale Discovery (MSD) on female flies. In both experiments, the following six groups of flies were examined: myow1118 ± BSA; myoArctic ± BSA; myoTandemAβ ± BSA. Conclusions from the studies are that the survival of AD flies could not be extended by adding 0.61 mM BSA to the food, rather the data showed a weak but significant toxic effect in the presence of BSA in the AD flies. However, MSD data showed a reduction of insoluble Aβ aggregates and an equilibrium shift from insoluble Aβ aggregates to soluble Aβ aggregates in the presence of BSA in the AD flies. Equilibrium shifts were particularly detectable in Myo-TandemAβ flies fed with BSA. In Myo-Arctic flies fed with BSA only reduction of insoluble Aβ could be detected. This shows that it is not the amount of Aβ aggregates that is decisive for toxicity, but rather the presence of specific aggregates that have toxic properties. If BSA shows good results in further studies, it could be used in the future to improve AD symptoms in patients. Drosophila melanogaster Alzheimer AD BSA Bovine serum albumin Human serum albumin HSA Toxicity Aβ survival assay MSD Meso Scale Discovery Arctic (Glu22Gly) TandemAβ oligomers fibrills GAL4-UAS TM6B CyO enterocytes Drosophila melanogaster bananfluga Alzheimers BSA Bovint serum albumin Aβ Amyloida plack Överlevnad MSD Meso Scale Discovery AD Toxicitet Arctic (Glu22Gly) TandemAβ HSA Humant serum albumin GAL4-UAS TM6B CyO fibriller oligomerer enterocyter Natural Sciences Naturvetenskap Other Chemistry Topics Annan kemi Biochemistry and Molecular Biology Biokemi och molekylärbiologi Other Biological Topics Annan biologi Genetics Genetik

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