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Physiological functions of muscarinic receptor M3
Urbánková, Anna ; Randáková, Alena (advisor) ; Rudajev, Vladimír (referee)
Muscarinic receptors belong to the family of G-protein coupled receptors. G-proteins are heterotrimeric GTP-binding proteins that transfer signals from receptors to effectors. Effectors change levels of second messengers in the cell. Individual subtypes of muscarinic receptors bind to various classes of G-proteins. According to the G-protein coupling, muscarinic receptors change levels of various second messengers. Individual subtypes of the muscarinic receptor also differ in location and function. The M3 muscarinic receptor subtype is located primarily on the periphery where it mediates smooth muscle contraction and endocrine and exocrine secretion. The goal of this bachelor thesis was to describe the tissue-specific signalling pathways of the M3 receptor and their physiological roles in the periphery as well as in the central nervous system. Further, the role of M3 receptors in several pathologies is described. Finally, the M3 receptors as a possible pharmacological target will be discussed. Key words: muscarinic receptors M3, cell signaling, G-proteins
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Effect of amyloid β on the function of endosomes and lysosomes
Tmějová, Monika ; Rudajev, Vladimír (advisor) ; Čočková, Zuzana (referee)
Alzheimer's disease is progressive neurodegenerative disease characterized by accumulation of amyloid β aggregates in brain tissue. Understanding the mechanisms of amyloid β pathogenesis and neuronal cell destruction is still not clear. The most toxic form of amyloid β are 42 aminoacids long oligomers that tends to cumulate and speed up disease progression. Membrane dynamics which affect protein degradation and recycling within the cell plays a criticale role in maintaining homeostasis. Vesicular trafficking plays fundamental role in balancing physiological level of amyloid β. Disruption of endolysosomal complex leads to cycle of disruptions within the cell which results in neuronal cell death. The main aim of this thesis was to look through different ways how amyloid β42 affects endolysosomal compartment. Results of our work confirmed toxic effect of amyloid on SH-SY5Y cell line and its ability to damage functions of lysosomes. We were not able to confirm amyloid β toxicity on endosomal function. Key words: amyloid β, Alzheimer disease, oligomers, plasma membrane, endocytosis, endosome, lysosome, neurotoxicity
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Physiological functions of muscarinic receptor M3
Urbánková, Anna ; Randáková, Alena (advisor) ; Rudajev, Vladimír (referee)
Muscarinic receptors belong to the family of G-protein coupled receptors. G-proteins are heterotrimeric GTP-binding proteins that transfer signals from receptors to effectors. Effectors change levels of second messengers in the cell. Individual subtypes of muscarinic receptors bind to various classes of G-proteins.According to the G-protein coupling, muscarinic receptors change levels of various second messengers. Individual subtypes of the muscarinic receptor also differ in location and function. The M3 muscarinic receptor subtype is located primarily on the periphery where it mediates smooth muscle contraction and endocrine secretion. The goal of this bachelor thesis was to describe the tissue-specific signalling pathways of the M3 receptor and their physiological roles in the periphery as well as in the central nervous system. Further, the role of M3 receptors in several pathologies is described. Finally, the M3 receptors as a possible pharmacological target will be discussed. Key words: muscarinic receptors M3, cell signaling, G-proteins
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The role of cholesterol in the pathogenesis of Alzheimer's disease
Tax, Martin ; Rudajev, Vladimír (advisor) ; Randáková, Alena (referee)
Alzheimer's disease is a neurodegenerative disorder and the most common form of dementia affecting a significant part of the aging population. It seems that the main cause of this disease is the accumulation of amyloid β (Aβ). Cholesterol is an important component of plasma membranes where it is essential for proper synapse function. Changes in its concentration are considered to be a risk factor for the onset and development of Alzheimer's disease. Data show that this lipid has an effect on Aβ synthesis and also has a role in Aβ cytotoxicity where it may promote the negative properties of Aβ or on the contrary can be protective against them.
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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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Potential role of opioids in neuroprotection
Gebauer, Martin ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
The opioids have been used by mankind for more than two millennia, but effect and mechanism of their action on the cells has been unveiling in the last few decades. The mechanism itself is often still unknown, but its effect is observed only. There are several groups of opioid receptors which are able to bind opioids. These groups are characterized by their differe nt affinity to opioids, in some cases by their different effects on cells and by their representation in the various areas in the CNS. Thus, the effects induces by these opioid are very different in many cases. This thesis summarizes the current knowledge about coronary heart disease and the potential of opioids for the prevention and their effect during ischemia, also summarizes the effects of morphine on the CNS. During ischemia δ-opioid receptors play a major role, because they inhibit or block the proapoptotic effects of ischemia on many levels. These receptors are also involved in inducing and maintaining the animal hibernation and protect animal's body against very harmful effects of hibernation, e.g lack of oxygen and nutrients. Morphine is opioid which has been used as anesthetic for longest time. It is well-known opioid and it has the most known derivates. This thesis also summarizes most significant effects of morphine on...
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Effect of chronic morphine treatment of rats on myocardial signaling systems regulated by trimeric G-proteins
Škrabalová, Jitka ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
It has recently been discovered that the effect of morphine can significantly reduce the tissue damage that occurs during myocardial ischemia. The molecular mechanisms by which morphine acts on the heart are still little understood. The aim of this thesis was to monitor the effect of chronic 27-day and 10-day administration of low (1 mg/kg/day) and high (10 mg/kg/ day) doses of morphine on the expression of selected G-protein-coupled receptors (GPCR) and on the expression and activity of adenylyl cyclase (AC). Chronic (27 days) morphine treatment reduced the expression of к-opioids receptors, but 10-day morphine exposure did not influence the expression of these receptors. Assessment of β1- and β2-AR by immunoblot technique did not show any significant change in the expression, but the more accurate determination of β-AR expression using the saturation binding studies revealed that 27-day treatment with high doses of morphine appreciable increased the total number of these receptors. Administration of high doses of morphine led to marked up-regulation of adenylyl cyclase (AC) isoforms V/VI, and the amount of AC decreased proportionally with the time of discontinuation of morphine administration. Low doses of morphine up- regulated AC only during 27-day administration. Chronic morphine exposure did...
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Endogenous opioids and their physiological significance
Jandová, Gabriela ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
This study examines the influence of endogenous opioid system on physiological processes. Opioid substances and their receptors are located not only in central but also in peripheral nervous systems, as well as in other tissues. Endogenous opioids are produced in the body and influence a wide-range of physiological functions. They are regulators of pain, emotions, breathing, memory, homeostatic functions, etc. Due to their diversity and variety of effects, they may have many possible medical uses, whether in the field of cardiology, anesthesiology or psychiatry. Since the opioid system influences many physiological processes, the understanding of its properties and functioning is prerequisite for deeper study of those processes. Therefore, the study of opioid system and new discoveries in this field receive a great deal of attention nowadays. Key words: Opioid system, endogenous opioids, receptors, nervous system, physiological functions, pain, emotions, breathing, memory, homeostasis
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Biocompatibility of porous NCD layers with neurons
Freislebenová, Hana ; Benson, Veronika (advisor) ; Rudajev, Vladimír (referee)
Nanodiamond is currently one of the most researched materials in the field of regenerative medicine in the study of treatment of neurodegenerative diseases. Due to direct interaction of this material with nerve tissue, it needs to be biocompatible with primary neurons. Furthemore, it is desirable for the used material to induce cell adhesion and stimulate the adherent cells to regeneration. This work evaluates the biocompatibility of porous boron-doped diamond layers with the culture of primary neurons. We compared the effect of diamond surface treatment by poly- D-lysine (PDL) coating on the adhesion and prosperity of the primary neuronal culture. We found that the tested nanodiamond layers are biocompatible with the primary neuronal culture. We further conclude that the PDL coating slightly increases the rate of cell adhesion to the surface but on the other hand induces greater adhesion of glial cells than the surface without PDL coating. Key words: nanodiamond, biocompatibility, adhesion, neurons
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