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Adenosine signaling: the role in neuroprotection and neurodegeneration
Hrušovská, Kateřina ; Novotný, Jiří (advisor) ; Kolář, David (referee)
The aim of this bachelor thesis is to describe basic and the most important mechanisms of adenosine signaling, especially in the central nervous system, where the purine nucleoside adenosine plays important role like significant neuromodulator. Strong release of adenosine to extracellular space may occur under some pathological conditions. Adenosine works throught his four receptors, which have very diverse functions. Some effects are neuroprotective - these are predominantly mediated throught the inhibitory A1 receptor, which can reduce neurotoxicity, others may also induce neurodegeneration, mainly due to increased activation of A2A receptors. This signaling system can be diversely modulated, for example by inhibition of enzymes, which can provide adenosine formation or degradation, blocking its transporters, by agonists or adenosine antagonists, or by inhibition of second messengers and various protein kinases by which adenosine affects cellular processes. Interactions of adenosine receptors with other types of receptors in the brain are also important. Adenosine and adenosine receptors can participate in neurodegenerative processes. A detailed understanding of the specific effects of adenosine can bring great progress in the treatment of neurodegenerative diseases. At present, intensive...
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Adenosin a nádorová imunoterapie
FREJLACHOVÁ, Andrea
The aim of this bachelor thesis was to study the immunosuppressive effects of adenosine and the use this knowledges in cancer immunotherapy. The impact of enzymatic removal of adenosine on efficacy of cancer immunotherapy was examined using murine pancreatic model Panc02.
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Přítomnost nízkomolekulárních imunomodulátorů ve slinách klíštěte \kur{Ixodes ricinus}
HAUSEROVÁ, Simona
Ticks use proteinaceous molecules contained in their saliva to suppress immune response of the host to complete their succesful feeding. In some ticks (e.g. Rhipicephalus sanguineus) presence of non-proteinaceous molecules was discovered. The aim of this work was to determine the amount of these molecules in the saliva of Ixodes ricinus tick. Namely, prostaglandin E2 and adenosine were analyzed. The second aim of this work was to evaluate the role of both low molecular weight components (or at least one of them) in the suppression of TNF-alfa cytokine production in suitable cells by ticks saliva.
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Microglia control adenosine A2A-receptor mediated astrogliosis
Svobodová, Magdaléna ; Mladěnka, Přemysl (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Magdaléna Svobodová Supervisor: Assoc. Prof. Přemysl Mladěnka, Ph.D. Assoc. Prof. Maria da Glória Correia da Silva Queiroz, Ph.D. Title of diploma thesis: Microglia control adenosine A2A-receptor mediated astrogliosis In the central nervous system, astrocytes and microglia are the main cells coordinating the inflammatory response. During inflammation, dying or temporarily damaged cells release ATP, as a danger-associated signal molecule, that contributes to the induction of astrogliosis and promotes clearance of the debris by immune cells such as microglia. Adenosine that results from ATP metabolism also stimulates astrogliosis. However, the effects of adenosine on astrogliosis may be more complex, since it also modulates microglia phenotype and microglia have been shown to prevent excessive astroglial proliferation mediated by nucleotides. In this context, ATP and adenosine are assumed as relevant signalling molecules in the control of astrogliosis and its modulation by microglia. However, it is still unknown whether and how microglia modulate adenosine-mediated astrogliosis. The present study aims to clarify the impact of microglia in the control of adenosine-induced astrogliosis. Two...
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Microglia control adenosine A2A-receptor mediated astrogliosis
Svobodová, Magdaléna ; Mladěnka, Přemysl (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Magdaléna Svobodová Supervisor: Assoc. Prof. Přemysl Mladěnka, Ph.D. Assoc. Prof. Maria da Glória Correia da Silva Queiroz, Ph.D. Title of diploma thesis: Microglia control adenosine A2A-receptor mediated astrogliosis In the central nervous system, astrocytes and microglia are the main cells coordinating the inflammatory response. During inflammation, dying or temporarily damaged cells release ATP, as a danger-associated signal molecule, that contributes to the induction of astrogliosis and promotes clearance of the debris by immune cells such as microglia. Adenosine that results from ATP metabolism also stimulates astrogliosis. However, the effects of adenosine on astrogliosis may be more complex, since it also modulates microglia phenotype and microglia have been shown to prevent excessive astroglial proliferation mediated by nucleotides. In this context, ATP and adenosine are assumed as relevant signalling molecules in the control of astrogliosis and its modulation by microglia. However, it is still unknown whether and how microglia modulate adenosine-mediated astrogliosis. The present study aims to clarify the impact of microglia in the control of adenosine-induced astrogliosis. Two...
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Adenosine metabolism and its role in cell physiology
Neumannová, Kateřina ; Novotný, Jiří (advisor) ; Hansíková, Jana (referee)
Adenosine is not just a major component of important molecules such as ATP, RNA or cAMP, but also has its own signaling function. Therefore, its extracellular level is strictly maintained by balance in its formation, degradation and transport. Both inside and outside the cell adenosine is formed mainly through degradation of ATP and is eliminated by two enzymes, adenosine kinase and adenosine deaminase. Transport of adenosine through the cell membrane is provided by nucleoside transporters, which are either equilibrative or concentrative according to the mechanism of transfer. All three processes described above contribute to maintaining adenosine level under normal conditions and its increase in pathological situations. Extracellular adenosine as a signal molecule binds to adenosine receptors (subtypes A1, A2A, A2B, A3) that affect many cellular signaling pathways via G-proteins. By these pathways adenosine regulates energy homeostasis, controls the function of various organs and also modulates the nervous and immune system and thus it may participate in a number of pathological processes. Pharmacological affecting of specific adenosine receptors or enzymes involved in its metabolism can serve as an effective therapy. Some drugs based on this system are already in use, others are being tested, and many...
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The influence of perinatal hypoxia on motoric development on laboratory rat and means of therapy
Vachovcová, Sylva ; Mareš, Pavel (advisor) ; Stuchlík, Aleš (referee)
Severe perinatal hypoxia represents a substantial brain injury in human newborns. This Diploma thesis is focused on long-term motor outcome of laboratory rat after moderate perinatal hypoxia. We described some behavioral test for detection motor development and presented the influence of perinatal hypoxia on central nervous system. We also discussed an effect of agonists and antagonists of adenosine A1 receptor in brain. The aim of an experimental part was an evaluation of long-term motor behavior in rats affected by perinatal hypoxia. To cause perinatal hypoxia we put pregnant female rats to a hypoxic (10% O2) normobaric room in 11th day of their gestation. The pregnant female rats stayed in hypoxic room until they gave a birth and 6 more days after birth with their litters. For classification of motor development we used battery of tests of motor coordination. These tests correspond to the level of development of the rat. Then a group of rats with perinatal hypoxia was treated by a single administration of an agonist of adenosine A1 receptor 2-chloro-N(6)- cyclopentyladenosin (CCPA) in postnatal day 14. The animals affected by perinatal hypoxia show motor deficits in 3 from 4 selected behavioral tests. Otherwise, this motor behavior was no longer detected in young adults. The rats affected by...
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Efekt ADGF-A RNAi na imunitní odpověď \kur{Drosophily melanogaster} po infekci parazitickou vosou
ŠNEBERGEROVÁ, Pavla
In previous studies the extracellular adenosine has been proved as an important signaling molecule controlling dynamics of the immune response in Drosophila melanogaster. In mammals the adenosine signaling and control is more complex process. Since there is a certain genetic and evolutionary conservation between mammals and invertebrates, Drosophila represents simple system how to study such a complex regulation in vivo. Mutations of adenosine receptor in all cells as well as downregulation of ENT2 in immune cells caused decrease of resistance of the immune system against Drosophila parazitoid. The aim of the thesis is to determine whether RNAi targeted against mRNA of adenosine deaminase ADGF-A, which degrades e-Ado under natural conditions, would have any effect on immune response.
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