Publication: Contribución al conocimiento de AMPK como diana terapéutica a través del descubrimiento de nuevos moduladores
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2017-06-26
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Universidad Complutense de Madrid
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Abstract
La proteína quinasa activada por AMP (AMPK) es un sensor de la energía celular que, una vez activado, juega un papel fundamental en muchos procesos que tienen lugar en la célula y que están encaminados a restaurar la homeostasis energética. Esta proteína activa e intensifica rutas y procesos catabólicos para generar ATP, como la β-oxidación de ácidos grasos y la autofagia, e inhibe procesos y rutas anabólicas que consumen energía, como la síntesis de ácidos grasos, colesterol y proteínas. Está presente en todos los organismos eucariotas, y en el caso de los humanos, se encuentra en prácticamente todos los tejidos y órganos: hígado, riñón, músculo y músculo esquelético, tejido vascular, neuronas, tejido adiposo, sistema inmunológico. Esta ubicuidad, entre especies, entre tejidos y entre rutas metabólicas la convierte en imprescindible en el correcto funcionamiento celular. Desde su descubrimiento, esta proteína viene concentrando un creciente interés en los campos de la química médica, la farmacología, la biología molecular y la medicina. Esto ha hecho que poco a poco avance nuestro conocimiento sobre las formas en las que esta proteína lleva a cabo su función, sobre sus mecanismos de activación y regulación y sobre la forma en que coordina unos y otros campos de la homeostasis, metabolismo energético, inmunología, crecimiento y ciclo celular, etcétera, para originar una respuesta cohesionada, y por tanto sana, a las situaciones de consumición de las reservas de energía. Además, resulta evidente que una proteína con un papel tan capital como AMPK debe estar involucrada en numerosas enfermedades. Su desregulación o funcionamiento anómalo por cualquier causa están asociados a patologías que pueden afectar a cualquier zona del organismo: desde el cáncer a enfermedades neurodegenerativas, pasando por la diabetes, el síndrome metabólico, la obesidad, el síndrome de Wolff-Parkinson-White y alteraciones vasculares. Y, como pasaba con su funcionamiento en condiciones sanas, cada vez tenemos una información más completa del inmenso abanico de alteraciones en las que AMPK está involucrada, en todas ellas desempeñando un papel importante...
AMP-activated proetin Kinase (AMPK) is a cellular energy sensor which, once active, plays a key role in many processes taking place in the cell and that are designed to restore energy homeostasis. This protein activates and intensifies catabolic routes and processes in order to generate ATP, such as fatty acids β-oxidation or autophagy, and inhibits energy-consuming anabolic routes and processes, such as fatty acids, cholesterol and proteins synthesis. It is present in all eukaryotic organisms, and in the case of humans, it is virtually present in all tissues and organs: liver, kidney, muscle and skeletal muscle, vascular tissue, neurons, adipose tissue, immune system. This ubiquity between species, tissues and metabolic pathways makes it essential in the proper cell function. Since its discovery, this protein has concentrated an increasing interest in the fields of medicinal chemistry, pharmacology, molecular biology and medicine. This has made advance our understanding about the ways in which this protein performs its function, about its activation and regulation mechanisms and about how it coordinates all the fields of homeostasis, energy metabolism, immunology, cellular growth and cycle, etc., to perform a cohesive and healthy response to events consuming the energy reserves. Furthermore, it is evident that a protein with such a central role must be involved in numerous diseases. Deregulation or malfunction because of any reason are associated with diseases that may affect to any part of the organism: from cancer to neurodegenerative diseases to diabetes, metabolic syndrome, obesity, Wolff-Parkinson- White syndrome and vascular alterations. And, as happen with its function in healthy conditions, we have an increasing information about the immense range of disorders in which AMPK is involved, playing an importante role in all of them...
AMP-activated proetin Kinase (AMPK) is a cellular energy sensor which, once active, plays a key role in many processes taking place in the cell and that are designed to restore energy homeostasis. This protein activates and intensifies catabolic routes and processes in order to generate ATP, such as fatty acids β-oxidation or autophagy, and inhibits energy-consuming anabolic routes and processes, such as fatty acids, cholesterol and proteins synthesis. It is present in all eukaryotic organisms, and in the case of humans, it is virtually present in all tissues and organs: liver, kidney, muscle and skeletal muscle, vascular tissue, neurons, adipose tissue, immune system. This ubiquity between species, tissues and metabolic pathways makes it essential in the proper cell function. Since its discovery, this protein has concentrated an increasing interest in the fields of medicinal chemistry, pharmacology, molecular biology and medicine. This has made advance our understanding about the ways in which this protein performs its function, about its activation and regulation mechanisms and about how it coordinates all the fields of homeostasis, energy metabolism, immunology, cellular growth and cycle, etc., to perform a cohesive and healthy response to events consuming the energy reserves. Furthermore, it is evident that a protein with such a central role must be involved in numerous diseases. Deregulation or malfunction because of any reason are associated with diseases that may affect to any part of the organism: from cancer to neurodegenerative diseases to diabetes, metabolic syndrome, obesity, Wolff-Parkinson- White syndrome and vascular alterations. And, as happen with its function in healthy conditions, we have an increasing information about the immense range of disorders in which AMPK is involved, playing an importante role in all of them...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Química Orgánica, leída el 08-07-2016