Chemical tools for the study of sphingolipid metabolism in diseases
[eng] The main goals of this PhD thesis are closely related within the field of CDases and their key role in the regulation of sphingolipid metabolism. Thus, the roles of ACER3 and AC in different human diseases are of valuable interest. However, research in this area has been hampered by the lack o...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/196740 |
| Acceso en línea: | https://hdl.handle.net/2445/196740 http://hdl.handle.net/10803/688044 |
| Access Level: | acceso abierto |
| Palabra clave: | Ciències de la salut Metabolisme Patologia Esfingolípids Medical sciences Metabolism Pathology Sphingolipids |
| Sumario: | [eng] The main goals of this PhD thesis are closely related within the field of CDases and their key role in the regulation of sphingolipid metabolism. Thus, the roles of ACER3 and AC in different human diseases are of valuable interest. However, research in this area has been hampered by the lack of specific inhibitors. For this reason, one of the objectives in this thesis was the discovery of specific inhibitors for AC and ACER3 displaying activity in intact cells. AC is highly expressed in several types of cancer, and its deficiency is correlated with the Farber’s disease. The existence of a method able to visualize the intracellular active form of AC, not the inactive one, is essential for the diagnosis of diseases associated with alterations in AC activity. Moreover, it is also important for the evaluation of the beneficial outcomes of therapeutic strategies. Hence, no methods have been yet presented to fulfill that aim, which hindered the development of therapeutic approaches based on chaperones due to the inability of imaging and following the existence of active AC in live cells. Activity-based probes (ABPs) have been proved useful in the visualization of active enzymes. Although few examples of ABPs for AC labelling have been reported, none of them was successfully used for live cell imaging of AC. Therefore, the other aim of this thesis was to develop an optimal ABP able to visualize the catalytically active (AC) in intracellular compartments of living cells. |
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