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Mitochondrial dysfunction in brain tumors
Rollerová, Kateřina ; Vaňátko, Ondřej (advisor) ; Zobalová, Renata (referee)
Brain tumors are one of the most serious pathologies of the central nervous system. Brain tumors are aggressive and very hard to treat due to the fragile nature of the nervous system, presence of blood-brain barrier and high recurrence rate. One of the hallmarks of brain tumors is mitochondrial dysfunction. Mitochondria are organelles involved in essential cellular processes, such as energy production, redox and calcium signaling, or the regulation of cell death. Structural and functional abnormalities, mutations in the mitochondrial genome and other mitochondrial dysregulations may cause disruptions in various cellular processes, such as production of reactive oxygen species, migration, proliferation, or regulation of cell death, promoting the development and/or maintenance of brain tumors. The goal of this thesis is to summarize current knowledge about mitochondrial dysfunction in brain tumors. Key words: brain tumors; mitochondria; mitochondrial dysfunction; Warburg effect; apoptosis; reactive oxygen species; isocitrate dehydrogenase
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Physiological principles of current therapeutic approaches in the treatment of Alzheimer's disease
Denisova, Elizaveta ; Rudajev, Vladimír (advisor) ; Veverová, Kateřina (referee)
Alzheimer's disease is a progressive neurodegenerative disease that affects millions of people worldwide. The pathology of Alzheimer's disease includes amyloid and tau hypothesis, mitochondrial dysfunction and neurodegeneration. Classical treatments for Alzheimer's disease include drugs targeting the cholinergic and glutamatergic systems, such as donepezil, galantamine, rivastigmine, and memantine. Diagnostic tools and techniques are constantly evolving to better identify and monitor the course of the disease. New approaches to the treatment of Alzheimer's disease include beta-amyloid-targeted therapies that seek to reduce the production or facilitate the clearance of these pathological peptides. Nutritional and lifestyle interventions, such as the potential effects of antioxidants on reducing oxidative stress, the neuroprotective effects of statins, and the potential benefits of a ketogenic diet for Alzheimer's patients, have become a key part of a multidisciplinary approach to treatment and are being explored as part of a comprehensive strategy to improve patients' quality of life. Key words: Alzheimer's disease, amyloid hypothesis, tau hypothesis, mitochondrial dysfunction, neurodegeneration, cholinergic system, glutamatergic system, new therapeutic approaches, nutrition, lifestyle.
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The inner mitochondrial membrane cristae biogenesis
Efimova, Iuliia ; Mráček, Tomáš (advisor) ; Petrů, Markéta (referee)
Invaginations of the inner mitochondrial membrane originate cristae - important structural and bioenergetic mitochondrial compartments. Long-term observations of mitochondrial ultrastructure uncovered cristae dynamics, but did not identify mechanisms of cristae formation and maintenance. This thesis summarizes results of latest research on molecular mechanisms of mitochondrial cristae biogenesis, which are conserved from fungi to mammals including human. The emphasis is put on major remodeling factors: F1Fo-ATP synthase dimers, MICOS complex, OPA1 protein and cardiolipin. Their defects lead to extensive changes on cristae level, as well as on mitochondrial, cellular and organismal levels. Various pathophysiological conditions and human mitochondrial diseases are related to these defects. More detailed research of cristae biogenesis is therefore of high significance, new findings could assist in the development of new treatments for mitochondrial disorders.
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Mitochondrial dysfunction and neurodegenerative diseases
Novotná, Veronika ; Herink, Josef (advisor) ; Kovařík, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Author: Bc. Veronika Novotná Supervisor: doc. MUDr. Josef Herink, DrSc. Title of diploma thesis: Mitochondrial dysfunction and neurodegenerative diseases The diploma thesis deals with mitochondrial dysfunction and neurodegenerative diseases and it is divided into two main parts. The first part summarized the classification of neurodegenerative diseases and general charakteristic of mitochondria.Then a describe of the processes of oxidative stress, excitotoxicity, apoptosis and briefly decribe the nervous system. The second part deals with description of mitochondrial dysfunction in selected nerodegenerative diseases. The recent studies refer to connection between mitochondrial dysfunctions and formation of neurodegenerative diseases. Keywords: excitotoxicity, mitochondrial dysfunction, neurodegenerative disorders, neuronal cell death, oxidative damage
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Physiologic and pathophysiologic aspects of selected endocrinopathies. Their relationship to adipose tissue matebolism and insulin resistance
Ďurovcová, Viktória ; Kršek, Michal (advisor) ; Saudek, František (referee) ; Štich, Vladimír (referee)
The pathogenesis of insulin resistance is a complex and still intensively studied issue. Endocrine and paracrine activity of the adipose tissue together with mi- tochondrial dysfunction are the most discussed potential factors included in the development of insulin resistance. In the first part of our study we examined the involvement of the adipose tissue and its secretory products in the etiopathogenesis of insulin resistance in patients with Cushing's syndrome, acromegaly and simple obesity. We focused on three important regulators of metabolic homeostasis - fibroblast growth factors 21 and 19 (FGF-21 and FGF-19) and adipocyte fatty acid binding protein (FABP-4). We found significantly elevated circulating levels of FGF-21 and FABP-4 ac- companying insulin resistance in both patients with simple obesity and patients with obesity connected to Cushing's syndrome, as compared to healthy controls. The concentrations of both substances were comparable between hypercortisolic and obese patients. This finding together with the absence of correlation be- tween the levels of FGF-21 resp. FABP-4 and cortisol suggest that the reason for elevation of their concentrations is obesity and its metabolic consequences themselves rather then the effect of hypercortisolism on FGF-21 and FABP-4 production. We found no...
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Intramembrane proteases and their medical significance
Deylová, Anna ; Stříšovský, Kvido (advisor) ; Macůrková, Marie (referee)
Intramembrane proteases are membrane enzymes whose active site is buried below the surface of the biological lipid membrane, and which cleave other membrane proteins within their transmembrane domains. They are divided into four families according to their catalytic residues - aspartate, serine (often called rhomboids), metalloproteases and the recently described glutamate proteases. By proteolytic cleavage inside lipid bilayer they affect many significant biological processes such as metabolism of lipids, cell proliferation and adhesion, regulation of developmental signaling, degradation of signal peptides, and membrane protein quality control. This work focusses on the role of intramembrane proteases in various diseases and biological mechanisms associated with pathological processes. These are specifically Alzheimer's disease, infection by unicellular parasites (Mycobacterium tuberculosis, Entamoeba histolytica and Plasmodium falciparum), maturation of hepatitis C virus, Bunyamwera virus and swine influenza virus, and mitochondrial dysfunction.
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Mitochondrial dysfunction and neurodegenerative diseases
Novotná, Veronika ; Herink, Josef (advisor) ; Kovařík, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Author: Bc. Veronika Novotná Supervisor: doc. MUDr. Josef Herink, DrSc. Title of diploma thesis: Mitochondrial dysfunction and neurodegenerative diseases The diploma thesis deals with mitochondrial dysfunction and neurodegenerative diseases and it is divided into two main parts. The first part summarized the classification of neurodegenerative diseases and general charakteristic of mitochondria.Then a describe of the processes of oxidative stress, excitotoxicity, apoptosis and briefly decribe the nervous system. The second part deals with description of mitochondrial dysfunction in selected nerodegenerative diseases. The recent studies refer to connection between mitochondrial dysfunctions and formation of neurodegenerative diseases. Keywords: excitotoxicity, mitochondrial dysfunction, neurodegenerative disorders, neuronal cell death, oxidative damage
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The influence of very-low calorie diet and pharmacologic interventions on adipose tissue metabolism in patients with type 2 diabetes mellitus and obesity.
Gregová, Monika ; Haluzík, Martin (advisor) ; Kunešová, Marie (referee) ; Žourek, Michal (referee)
(EN) Obesity and type 2 diabetes mellitus (T2DM) are among metabolic disease with increasing incidence and prevalence. Last decade has been devoted to intensive research focused on pathophysiological mechanisms underlying development of these diseases. Besides environmental factors, lifestyle and amount and composition of food, adipose tissue is a key player in the pathogenesis of obesity and its metabolic complications including insulin resistance (IR) and T2DM. Primary aim of our work was to evaluate the role of recently discovered adipokine omentin and the role of mitochondrial dysfunction in subcutaneous adipose tissue (SCAT) and in peripheral monocytes (PM) in patients with obesity and T2DM with respect to the development of insulin resistance and diabetes. A total number of 118 subjects enrolled in the study were divided into three groups: patients with obesity and T2DM (T2DM group), obese non-diabetics (OB) and healthy lean subjects as a control group (KO). Study subjects underwent several types of interventions - 2 to 3 weeks of very-low calorie diet (VLCD, energy intake 600 kcal per day), regular physical activity program or bariatric surgery (laparoscopic sleeve gastrectomy, LSG). Results indicate that low serum omentin concentrations may contribute to development of obesity-associated...
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The inner mitochondrial membrane cristae biogenesis
Efimova, Iuliia ; Mráček, Tomáš (advisor) ; Petrů, Markéta (referee)
Invaginations of the inner mitochondrial membrane originate cristae - important structural and bioenergetic mitochondrial compartments. Long-term observations of mitochondrial ultrastructure uncovered cristae dynamics, but did not identify mechanisms of cristae formation and maintenance. This thesis summarizes results of latest research on molecular mechanisms of mitochondrial cristae biogenesis, which are conserved from fungi to mammals including human. The emphasis is put on major remodeling factors: F1Fo-ATP synthase dimers, MICOS complex, OPA1 protein and cardiolipin. Their defects lead to extensive changes on cristae level, as well as on mitochondrial, cellular and organismal levels. Various pathophysiological conditions and human mitochondrial diseases are related to these defects. More detailed research of cristae biogenesis is therefore of high significance, new findings could assist in the development of new treatments for mitochondrial disorders.
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Physiologic and pathophysiologic aspects of selected endocrinopathies. Their relationship to adipose tissue matebolism and insulin resistance
Ďurovcová, Viktória ; Kršek, Michal (advisor) ; Saudek, František (referee) ; Štich, Vladimír (referee)
The pathogenesis of insulin resistance is a complex and still intensively studied issue. Endocrine and paracrine activity of the adipose tissue together with mi- tochondrial dysfunction are the most discussed potential factors included in the development of insulin resistance. In the first part of our study we examined the involvement of the adipose tissue and its secretory products in the etiopathogenesis of insulin resistance in patients with Cushing's syndrome, acromegaly and simple obesity. We focused on three important regulators of metabolic homeostasis - fibroblast growth factors 21 and 19 (FGF-21 and FGF-19) and adipocyte fatty acid binding protein (FABP-4). We found significantly elevated circulating levels of FGF-21 and FABP-4 ac- companying insulin resistance in both patients with simple obesity and patients with obesity connected to Cushing's syndrome, as compared to healthy controls. The concentrations of both substances were comparable between hypercortisolic and obese patients. This finding together with the absence of correlation be- tween the levels of FGF-21 resp. FABP-4 and cortisol suggest that the reason for elevation of their concentrations is obesity and its metabolic consequences themselves rather then the effect of hypercortisolism on FGF-21 and FABP-4 production. We found no...
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