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The role of microglia and astrocytes in Alzheimer's disease
Pospíšilová, Eva ; Telenský, Petr (advisor) ; Svoboda, Jan (referee)
Alzheimer's disease is a neurodegenerative disease that affects the central nervous system and is characterized mainly by problems with memory abilities. With the more aging population, the number of patients with this disease is gradually increasing, so Alzheimer's disease research is becoming one of the main priorities of today's health care. Although the research has been going on for more than a century, the exact causes of the Alzheimer's disease are still unclear. For a long time, the main role was attributed to the pathology of amyloid β and tau protein, the basic pathophysiological features of this disease, but in recent years, it has become clear that microglia and astrocytes also play an important role. These glial cells affect the amount of amyloid β and the hyperphosphorylated tau protein, but they are also crucial for maintaining homeostasis of the central nervous system. Activation of microglia and astrocytes in Alzheimer's disease can lead to disruption of the physiological functions of these neuroglia, and thus to problems with the removal of amyloid and tau protein, but also to the induction of chronic neuroinflammation. This work aims to summarize and organize the basic knowledge about the role of microglia and astrocytes in Alzheimer's disease, while focusing mainly on their role...
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Tau protein, a biomarker of Alzheimer's disease: in vitro phosphorylation and tau-reactive antibodies characterization
Hromádková, Lenka ; Bílková, Zuzana (advisor) ; Fialová, Lenka (referee) ; Krejsek, Jan (referee)
Tau protein, a microtubule-associated protein localized in axonal projections of neurons, is a key molecule in the pathology of Alzheimer's disease (AD), the most common cause of dementia in the elderly population. Tau belongs to the group of natively unfolded proteins without globular structure and is prone to numerous posttranslational modifications (PTMs). Under pathological conditions, abnormal PTMs and misfolding of tau protein occurs and leads to oligomerization and aggregation into paired helical filaments forming neurofibrillary tangles, the histopathological hallmark of AD. Currently available drugs applied in AD treatment can only slow the disease progression and those, which halt the AD-specific neurodegenerative processes, are still missing. Very promising and evolving therapeutic approach is immunotherapy, and even immunomodulation by administration of intravenous immunoglobulin (IVIG) products, a reservoir of natural antibodies from the plasma of healthy donors, has been already tested. The discovery of naturally occurring antibodies directed to tau (nTau-Abs) in body fluids of both AD and healthy subjects and their presence in IVIG begin the investigation of their therapeutic potential. Considering a wide range of possible modifications of tau and of various tau species (oligomers,...
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Membraneless organelles in eukaryotic cells
Beránková, Pavla ; Libusová, Lenka (advisor) ; Bařinka, Cyril (referee)
Membraneless organelles (MLOs) are a newly described type of cellular compartments. They consist of protein and nucleic acid molecules that undergo liquid-liquid phase separation (LLPS). MLOs are able to fulfill unique biological roles, because they are highly dynamic and their composition can be effectively regulated. Composition and function of these formations are swiftly being elucidated. The work summarizes the basic principles of LLPS in living organisms and further focuses on several types of MLOs functionally connected to microtubules (MTs). Their recurrent feature is the ability to nucleate MTs. This eventual role corresponds well with their high temporal and spatial dynamics.
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New insights on tau protein aggregation and the spreading of tau pathology in Alzheimer's disease
Pribiš, Matej ; Růžička, Jiří (advisor) ; Telenský, Petr (referee)
More than 100 years have passed since the original description of a "peculiar" disease of cerebral cortex by Dr. Alzheimer. Lots of discoveries on this disease and its cellular and molecular correlates has been done since then, the disease, however, up to this day resists most of the causal attempts of treatment. The major component of silver stained tangled bundles of fibrils that Alzheimer observed under his microscope has been identified as a microtubule associated protein tau and it has been shown to be a crucial part of many other neurodegenerative disorders, which were collectively named tauopathies. However, even after such a long time, the exact role of tau in neuronal physiology and pathology remains rather obscure. According to the latest research, it even seems that some of the widely accepted truths might require more closer observation and validation. The aim of this thesis is to sum up and clarify the important aspects of the mechanism of tau aggregation, the basic factors that influence it and its transcellular movement as a mechanism of pathology spreading. Keywords: aggregation, pathology spreading, tauopathy, Tau protein iii
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Tau protein, a biomarker of Alzheimer's disease: in vitro phosphorylation and tau-reactive antibodies characterization
Hromádková, Lenka ; Bílková, Zuzana (advisor) ; Fialová, Lenka (referee) ; Krejsek, Jan (referee)
Tau protein, a microtubule-associated protein localized in axonal projections of neurons, is a key molecule in the pathology of Alzheimer's disease (AD), the most common cause of dementia in the elderly population. Tau belongs to the group of natively unfolded proteins without globular structure and is prone to numerous posttranslational modifications (PTMs). Under pathological conditions, abnormal PTMs and misfolding of tau protein occurs and leads to oligomerization and aggregation into paired helical filaments forming neurofibrillary tangles, the histopathological hallmark of AD. Currently available drugs applied in AD treatment can only slow the disease progression and those, which halt the AD-specific neurodegenerative processes, are still missing. Very promising and evolving therapeutic approach is immunotherapy, and even immunomodulation by administration of intravenous immunoglobulin (IVIG) products, a reservoir of natural antibodies from the plasma of healthy donors, has been already tested. The discovery of naturally occurring antibodies directed to tau (nTau-Abs) in body fluids of both AD and healthy subjects and their presence in IVIG begin the investigation of their therapeutic potential. Considering a wide range of possible modifications of tau and of various tau species (oligomers,...
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Geny a Alzheimerova choroba, možnosti diagnostiky
KOUDELKOVÁ, Kateřina
The aim of this work is to summarize findings about Alzheimer´s disease, which is the most common neurodegenerative disorder, its pathophysiology, epidemiology, risk factors, treatment options and genetics of disease. Further aim was to describe diagnostic options that are important to confirm the diagnosis of Alzheimer´s disease and to timely iniciation of treatment.
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Glial cells and their role in Alzheimer disease
Eliášová, Barbora ; Anděrová, Miroslava (advisor) ; Kazantsev, Dmitry (referee)
Alzheimer's disease is a neurodegenerative disorder, affecting mostly elderly people. It causes memory impairment and modifies the ability to talk, learn and make decisions. These are gradually getting worse until the patient loses them completely. Alzheimer's is the most common form of dementia worldwide, however until these days there is no cure. The main reason for this is that mechanisms and causes of this disease are still not utterly understood. Besides the neurodegeneration caused by aggregation of βamyloid protein and hyperphosphorylated tau protein, glial cells of central nervous system play also important role in the Alzheimer's disease. Astrocytes, microglia, oligodendrocytes and recently discovered synantocytes ensure various functions necessary for correct functioning of the brain and damage of these cells can be fatal. During a neurodegenerative disorder such as Alzheimer's, they are able to improve the course of the disease but also do the contrary and aggravate it by malfunctioning or losing one or even more of their functions. Key words: Alzheimer's disease, β amyloid, tau protein, astrocytes, microglia, oligodendrocytes, synantocytes
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The preparation of recombinant tau protein and it's usage for the detection of Alzheimer disease
Kolářová, Michala ; Hofbauerová, Kateřina (advisor) ; Fialová, Lenka (referee)
Currently a grate emphasis is being put on accurate and early diagnosis of Alzheimer's disease (AD), which is important for the introduction of treatments that could postpone the onset of the disease. Antibodies against tau protein appear to be suitable biomarkers for early diagnosis of AD. Therefore, this work deals firstly with preparation of human recombinant tau protein in bacteria and its subsequent use in determining levels of antibodies in blood serum of patients with AD and in normal older persons. A preparation of the tau protein in sufficient purity was achieved for the antibodies measurment by ELISA method and results were statistically analyzed using nonparametric methods. Results were compared with data from Mgr. Jany Švarcové obtained by measuring antibodies in serum of patients with AD and normal elderly using an commercial bovine tau protein. According to the analysis there are differences between the data obtained from human and the bovine tau protein. It was proven that patients with AN have lower levels of antibodies against tau protein than healthy seniors. Recombinant human tau protein was also used to immunize rabbits. The ELISA method confirmed the creation of antibodies against human tau protein in rabbits.
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