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The role of cellular senescence in carcinogenesis and aging of the brain
Paroubková, Michaela ; Hodný, Zdeněk (advisor) ; Horníková, Daniela (referee)
The risk of developing many pathological conditions and ageing-releated diseases increases persistently throughout a lifetime. A dramatic increase in the number of people suffering from one of these diseases, such as atherosclerosis, Alzheimer's disease or Parkinson's disease, is caused by constant elevation of human life's length due to advancements in modern medicine and changes in life style. Several recent studies have demonstrated that senescent cells accumulate in aged and ill tissues. Senescent cells are metabolically active, but unable of proliferation and unlike the terminally differented cells, they secrete many factors that contribute to the transformation of the tissue microenviroment. The role of senescence as anticancer barier is known for a long time, but its importance in physiological processes and aging is mainly a matter of a recent time. While there is also a lot of studies focusing on cellular senescence in peripheral tissues, their involvement in or contribution to cognitive decline with aging of the central nervous system (CNS) remains relatively unknown. Recent data of many laboratories suggest that senescence-associated secretory phenotype of the non-neuronal senescent cells in brain can cause chronic level of inflammation and thus accompany aging and ageing-related...
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MAP code and regulation of microtubule-based processes
Karhanová, Adéla ; Lánský, Zdeněk (advisor) ; Tomášová, Štěpánka (referee)
Microtubule associated proteins (MAPs) are considered as key regulators of molecular trafficking in cells. Even though their malfunctioning results in severe pathologies, such as neurodegenerative disorders, the regulatory roles of these proteins remain under debate. Since MAPs bind to the cytoskeleton, this structure has to be vital for the function of MAPs. Microtubules, a highly dynamic type of cytoskeletal structure, have been given extra attention due to their association with cell division and vital functions in neurons. Microtubules can undergo post-translational modifications that affect molecular motors as well as binding of other proteins, such as MAPs. Whether post-translational modifications of microtubules regulate the distribution of MAPs is so far not sufficiently documented. However, MAPs have been shown to cooperatively form cohesive envelopes on the microtubules and thereby regulate the access of motors and severing enzymes. As there are many types of MAPs and they are mutually exclusive, a hypothesis of a regulatory 'MAP code' emerged recently in the literature. Using available literature, this review will try to introduce the new model of MAP code and provide some background information on previous research on this topic.
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The role of biofluid biomarkers in the differential diagnosis of neurodegenerative diseases
Katonová, Alžbeta ; Čechová, Kateřina (advisor) ; Mrózková, Petra (referee)
Until recently, the diagnosis of Alzheimer's disease and other neurodegenerative diseases was dependent only on clinical expression, the definitive confirmation of which was possible only post- mortem. Currently, biofluid biomarkers represent a reliable source for the diagnosis of serious neurodegenerative diseases already during the patient's lifetime. The identification of reliable biomarkers is essential for increasing diagnostic accuracy, monitoring the clinical condition, more precise selection of individuals for clinical trials and the associated development of causal treatment. The aim of the bachelor's thesis was to conduct a thorough literature review focusing on clinically and experimentally used biological markers in the diagnosis of neurodegenerative diseases and their role in the pathophysiology of these diseases. Key words: Neurodegenerative diseases, biomarkers, proteinopathies, neurocognitive impairment, cognition
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Immunomodulatory properties of mesenchymal stem cells from patients with amyotrophic lateral sclerosis and healthy donors
Matějčková, Nicole
Mesenchymal stem cells (MSC) possess a multilineage differentiation potential and have the ability to regulate reactivity of the immune system. They are usually isolated and expanded from the bone marrow, adipose tissue or umbilical cord. MSC represent promising cell population for the treatment of some severe diseases, such as amyotrofic lateral sclerosis (ALS), due to the combination of regenerative and immunomodulatory properties. The aim of this study is to compare MSC from ALS patients and healthy donors in their phenotype, proliferative activity and mainly their immunomodulatory properties. The assessment of impact of the disease on the properties of MSC is important for their autologous use in clinical trials. In this study we used MSC isolated from bone marrow of 14 ALS patients and 15 patients undergoing mostly orthopedic surgery as control group. We also used MSC stimulated for 24 hours by poinflammatory cytokines. Cells were compared in terms of immunophenotype, differentiation in adipocytes and osteoblasts, metabolic activity, expression of selected genes for immunomodulatory molecules and for inhibition of lymphocyte proliferation. Further experiments were focused on evaluation of immunomodulatory properties of MSC. The effect of MSC on peripheral blood mononuclear cells stimulated...
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Speech intervention for adults with dementia
Pavlíková, Markéta ; Klenková, Jiřina (referee)
Univerzita Karlova Pedagogická fakulta Katedra speciální pedagogiky RIGORÓZNÍ PRÁCE Logopedická intervence u dospělých osob s demencí Speech therapy for adults with dementia Mgr. Markéta Pavlíková Konzultant práce: doc. PaedDr. Jiřina Klenková, PhD. Studijní program: Integrované studium speciální pedagogiky Studijní obor: Speciální pedagogika 1 ABSTRACT The thesis describes speech intervention for adults with dementia. The aim of the work and the research is to analyze speech intervention for adults with dementia and family cooperation in clinical speech therapy. The research is conducted through evaluation of questionnaires filled in by family members of patients studied and the subsequent evaluation of the benefits of speech therapy intervention provided both clinical speech therapist and trained family members. When processing techniques were used document analysis, analysis of results of operations, interviews with family members and observation. The aim of the thesis is to demonstrate, how much they may be useful interested, informed and cooperating family and how they can be routed speech therapy. KEYWORDS speech therapy, communication, intervention, neurodegenerative diseases, dementia, Alzheimer's disease, family
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The role of cellular senescence in carcinogenesis and aging of the brain
Paroubková, Michaela ; Hodný, Zdeněk (advisor) ; Horníková, Daniela (referee)
The risk of developing many pathological conditions and ageing-releated diseases increases persistently throughout a lifetime. A dramatic increase in the number of people suffering from one of these diseases, such as atherosclerosis, Alzheimer's disease or Parkinson's disease, is caused by constant elevation of human life's length due to advancements in modern medicine and changes in life style. Several recent studies have demonstrated that senescent cells accumulate in aged and ill tissues. Senescent cells are metabolically active, but unable of proliferation and unlike the terminally differented cells, they secrete many factors that contribute to the transformation of the tissue microenviroment. The role of senescence as anticancer barier is known for a long time, but its importance in physiological processes and aging is mainly a matter of a recent time. While there is also a lot of studies focusing on cellular senescence in peripheral tissues, their involvement in or contribution to cognitive decline with aging of the central nervous system (CNS) remains relatively unknown. Recent data of many laboratories suggest that senescence-associated secretory phenotype of the non-neuronal senescent cells in brain can cause chronic level of inflammation and thus accompany aging and ageing-related...
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Mitophagy in Huntington's Disease
Šonský, Ivan ; Hansíková, Hana (advisor) ; Macůrková, Marie (referee)
Mitochondrial dysfunctions contribute to the progression of many neurodegenerative diseases, including Huntington's disease (HD). In HD, mutation in the huntingtin gene (HTT) results in the expansion of CAG repeats, causing the growth of the polyglutamine tract. This growth is responsible for the gain of toxicity function of the protein. The turnover of dysfunctional and damaged mitochondria is mediated via mitophagy - a selective form of autophagy. Additionally, mitophagy impairments have recently been described to play a key role not only in neurodegenerative diseases. The protrusion of mitophagy results in the clustering of defective mitochondria, organelles which are responsible for fulfilling the energetic demands of neural cells. The most distinctive impact of the impairment is on the striatal medium spiny neurons and results in the development of motor and cognitive dysfunctions. This thesis describes how HD affects mitophagy and reveals the biggest obstacle of mitophagy - disruption of mitochondria targeting into emerging autophagosomes caused by the abnormal interaction of mHTT and p62. Induction of mitophagy at this stage could be crucial for the future therapeutic research of HD. Generally, initiation of mitophagy could become a relevant therapeutic target for many other...
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Extracellular vesicles derived from mesenchymal stem cells and their use in the treatment of neurological disorders
Kratochvílová, Anna ; Hájková, Michaela (advisor) ; Holada, Karel (referee)
Extracellular vesicles (EVs) are cell-derived membrane vesicles, which represent an important part of intercellular communication by transferring cytosolic proteins, lipids, and RNAs between cells. It has been proved that mesenchymal stem cells (MSCs) are potent producers of EVs with a therapeutic effect comparable to their parental cells. Moreover, recent findings suggest that EVs may strongly contribute to their physiological function. The aim of this thesis is to introduce extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) as a novel cell-free alternative to the cell-based therapy and focus on their neuroprotective properties studied in various neurological diseases.
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Immunomodulatory properties of mesenchymal stem cells from patients with amyotrophic lateral sclerosis and healthy donors
Matějčková, Nicole
Mesenchymal stem cells (MSC) possess a multilineage differentiation potential and have the ability to regulate reactivity of the immune system. They are usually isolated and expanded from the bone marrow, adipose tissue or umbilical cord. MSC represent promising cell population for the treatment of some severe diseases, such as amyotrofic lateral sclerosis (ALS), due to the combination of regenerative and immunomodulatory properties. The aim of this study is to compare MSC from ALS patients and healthy donors in their phenotype, proliferative activity and mainly their immunomodulatory properties. The assessment of impact of the disease on the properties of MSC is important for their autologous use in clinical trials. In this study we used MSC isolated from bone marrow of 14 ALS patients and 15 patients undergoing mostly orthopedic surgery as control group. We also used MSC stimulated for 24 hours by poinflammatory cytokines. Cells were compared in terms of immunophenotype, differentiation in adipocytes and osteoblasts, metabolic activity, expression of selected genes for immunomodulatory molecules and for inhibition of lymphocyte proliferation. Further experiments were focused on evaluation of immunomodulatory properties of MSC. The effect of MSC on peripheral blood mononuclear cells stimulated...
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Clinical applications of stem cells for the treatment of neurodegenerative diseases of CNS
Jančová, Pavlína ; Kubinová, Šárka (advisor) ; Heřmánková, Barbora (referee)
Stem cells have a huge therapeutic potential due to their ability to differentiate in multiple tissues. They could be used for neurodegenerative diseases treatment, which are typical for loss of specific groups of neurons, progressive course and lack of effective treatment due to their complicated pathophysiology, only therapies for elongation and simplification of patients' life are available. This thesis summarizes results of completed clinical studies and informs about ongoing studies, in which stem cell treatments are used for selected neurodegenerative diseases. Stem cell therapy for multiple sclerosis and amyotrophic lateral sclerosis have a long history, some of the studies has proven therapeutic efficiency of stem cells. We don't know much about effect of stem cell treatment for patients with Alzheimer's and Parkinson's diseases, because first clinical studies were finished recently. But all clinical trials have proven safety of stem cell treatment. Replacement of damaged neurons haven't been reached yet, just protection of remaining neurons by neurotrophic and immunomodulatory factors secreted by stem cells. Keywords: neurodegenerative diseases, stem cells, clinical trials, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease
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