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Interaction of amyloid β with neuronal membrane proteins
Manová, Blanka ; Rudajev, Vladimír (advisor) ; Černá, Barbora (referee)
Amyloid b peptide is cleaved from the amyloid precursor protein by b and γ secretases. According to the amyloid hypothesis i tis the main cause of the early pathogenetic events of Alzheimer's disease (AD) which is the most common neurodegenerative disease in the world without an effective treatment. The main pathogenesis of AD is considered to be the loss of synapses, disruption of neuronal plasticity and neurodegeneration. Amyloid b can bind directly to the membrane or mediate neuronal damage indirectly via toxic inflammatory mediators (e.g., reactive oxygen intermediates, nitric oxide and cytokines) by activating microglia and astrocytes. In addition to interacting with various membrane receptors, Ab can also bind to the cell surface directly, disrupting membrane integrity or forming selective cation channels. This thesis summarizes key interactions with membranes of synapses and mechanisms of amyloid- induced toxicity through receptors.
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The role of the cellular prion protein in the cells of the immune system
Havlík, Martin ; Holada, Karel (advisor) ; Pačes, Jan (referee) ; Pačes, Jan (referee)
Prion protein (PrPC) is connected with the origin of transmissive spongiform encephalopathies (TSEs), fatal diseases that are on the molecular level based on the conversion of the cellular form of prion protein, PrPC, into the infectious form, PrPTSE. This isoform, exhibiting increased resistance against proteases and common decontamination methods, accumulates in tissues and causes degenerative damages of the central nervous system. Potential physiological function of PrPC in cells remains unclear, though many efforts have been focused on this research area in past years. Expression of PrPC was detected especially in neurons, high levels of PrPC are also present in different types of cells of immune system. Whereas some immunocompetent cells were widely examined, the relationship of PrPC with the function of others was not studied. PrPC probably plays a role in differentiation and activation of some immune cells, participates in regulation of cytokine production and other immune processes, affects grow of CD4+ T-cell population and also takes a part in formation of secondary lymphatic organs. This bachelor thesis is focused on summarization of existing knowledge describing the role of the cellular prion protein in cells of immune system, which is important also from the point of view of diagnosis...
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Role of expression of cellular prion protein in the differentiation of neuronal cell lines
Kučerová, Johanka ; Holada, Karel (advisor) ; Janoušková, Olga (referee)
Cellular prion protein (PrPC ) is a membrane bound glycoprotein. The protein is expressed in all vertebrates, mainly in the nervous system, but it is present also in the cells of gastrointestinal tract, bone marrow, germ cells and heart. PrPC is necessary for pathogenesis of prion diseases, which are deadly and without the possibility of therapy. The pathogenic isoform of prion protein is formed by changing of secondary structure of PrPC and it's the main constituent of infectious prion particles. Pathological form of prion protein accumulates in brain of infected patients and this process is associated with neurodegradation. Physiological function of PrPC is poorly understood. Knock-out of the PrPC gene (PRNP) is not connected with any noticeable phenotype. Potential functions of PrPC are dispersed, protein may have antiapoptotic effect, it can be involved in ions metabolism or in protection against oxidative stress. Latest results show, that PrPC can play important role in cell differentiation. During the differentiation PrPC can influence the development of cells and their typing. It could affect cell cycle and have an influence on formation of nervous system. Aim of the present study was to elucidate, whether the down-regulation of PrPC or infection with prions has an impact on differentiation of...
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Role of prion proteins at differentiating cells
Kučerová, Johanka ; Holada, Karel (advisor) ; Drbal, Karel (referee)
Cellular prion protein (PrPC) is well known for its pathological isoform PrPSc, widely believed to be the infectious agent of the prion diseases, which include Bovine spongiform encephalopathy (BSE), scrapie and Creutzfeldt-Jakob disease. The physiological role of PrPC is poorly understood, but its involvement in the regulation of apoptosis, adhesion molecules, antioxidant, or signal molecules, has been described. Despite of these findings, it hasn't been proven, that the protein is necessary for normal development of mice. However, the protein was shown to be essential for regeneration of hematopoietic stem cells after exposure to lethal stress conditions. Expression of PrPC may have an effect on the proliferation and differentiation of cells by helping them keep the proliferative activity, or slow spontaneous differentiation. The quantity of the protein correlates positively or negatively with expression of transcription factors such as Oct4/Nestin, which are essential for development in embryogenesis. Its expression also regulates transition of cells from G1 phase to S phase of the cell cycle. This bachelor thesis is focused on published results describing the influence of PrPC on cellular proliferation and differentiation.
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Prionové proteiny a jejich interakce s těžkými kovy
Sedláčková, Eliška
Prion proteins are infectious glycoproteins that do not contain nucleic acids. Their specific function in the brain is not yet fully understood. Conversion of the cellular form of prion protein (PrPC) into the pathological isoform (PrPSc) is regarded as the cause of neurodegenerative diseases. PrPC is a glycoprotein that interacts with many divalent metal ions, particularly Cu2+ and Zn2+. Another protein having the ability to bind metals, is also metallothionein (MT), which consists of several specific forms. Regarding formation of neurodegenerative diseases is significant metallothionein isoform MT-3 occuring in the brain. One of the MT-3 functions in the brain is its participation in maintaining of the optimal concentration of metal ions. The aim of this study was to verify the presence of expression PrPC or MT-3 genes in E. coli bacterial cells. Furthermore, we investigated the effect of metal additions on E. coli bacterial culture expressing PrPC or MT-3 protein. In the end we focused on determining the total concentration of MT in E. coli bacterial cells expressing the PrPC or MT-3 protein. Any determination was compared to a standard E. coli BL21 (DE3) strain.
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Detekce prionových proteinů a jejich interakce s kovy a metalothioneinem
Cardová, Alžběta
Prion diseases are formed by a conformational change of prion-like protein (PrPC) with alfa-helix structure to the pathological isoform - prion (PrPSc) which acquires beta-sheet structure. PrPC physiological properties in the brain are insufficiently described but there is an assumption of its affinity to metal ions. Another protein with metal-binding ability is metallothionein (MT). Brain specific isoform of MT is called MT-III and it is assumed to participate in maintenance of metal ions concentration in the brain. Aim of this study was to prepare recombinant human PrPC in E. coli. Furthermore, this protein was used to detect interactions between metal ions (Cu, Zn), MT and PrPC by differential pulse voltammetry method. The final part was devoted to the MT-III determination in different genotypes of prion-infected and non-infectious mouse brain tissues.
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