Publication: Regulación de sistema ubiquitina-proteasoma por los receptores purinérgicos en el sistema nervioso central
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2018-02-06
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Universidad Complutense de Madrid
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Abstract
Los nucleótidos, que se comportan como neurotransmisores en el SNC, se encuentran implicados en una gran variedad de procesos fisiológicos y patológicos (Bodin & Burnstock 2001). Este papel como neurotransmisores se debe a que pueden activar diferentes receptores específicos de la membrana celular, denominados receptores purinérgicos P2 (Burnstock 2007). Estos receptores se dividen en dos grupos: receptores ionotrópicos (P2X1-7) y receptores metabotrópicos (P2Y1,2,4,6,11-14) (Burnstock et al 2012). Los receptores metabotrópicos P2Y se expresan en los diferentes linajes celulares del SNC donde regulan una gran variedad de procesos fisiológicos como la proliferación, crecimiento o supervivencia celular (Khakh & Burnstock 2009). Dentro de los receptores P2Y, el receptor P2Y2 posee unas características estructurales especiales que le permiten interaccionar tanto con integrinas como con otros receptores, lo cual hace que esté implicado en numerosos fenómenos fisiológicos y patológicos (Weisman et al 2012). De hecho, se ha postulado que el receptor P2Y2 representa una prometedora diana terapéutica para el tratamiento de algunas enfermedades. El papel neuroprotector asociado a dicho receptor ha sido observado principalmente bajo condiciones de neuroinflamación, estrés oxidativo y en enfermedades neurodegenerativas (Weisman et al 2012). Normalmente, estas situaciones se encuentran asociadas a un aumento de la cantidad de proteínas mal plegadas en el interior celular, hecho relacionado a su vez con un mal funcionamiento del Sistema Ubiquitina-Proteasoma (UPS) (Dantuma & Lindsten 2010). El UPS es el principal sistema encargado de controlar la proteostasis celular (Kaushik & Cuervo 2015), degradando de una manera específica y selectiva la mayoría de las proteínas intracelulares. Mediante la acción coordinada de las enzimas E1, E2 y E3, la proteína a degradar será marcada con una cadena de moléculas de Ubiquitina para posteriormente ser degradada por el proteasoma (Hershko & Ciechanover 1998)...
Nucleotides, which act as neurotransmitters in the Central Nervous System (CNS), are involved in several physiological and pathological processes (Burnstock 2007). This role as neurotransmitters is due to their capacity to activate different specifics receptors in the cellular membrane denominated P2 purinergic receptors,. These receptors are divided into two groups: ionotropic receptors (P2X1-7) and metabotropic receptors (P2Y1,2,4,6,11-14) (Burnstock et al 2012). Metabotropic P2Y receptors are expressed in the different cellular lineages that form the CNS where they regulate a wide variety of physiological processes such as cell proliferation, growth or survival (Khakh & Burnstock 2009). Within P2Y receptors, the P2Y2 receptor has special structural characteristics that allow it to interact with both integrins and others receptors, which are related to several physiological and pathological phenomenon (Weisman et al 2012). Hence, it has been described that under neuroinflammation conditions, oxidative stress and neurodegenerative disorders, P2Y2 receptor may play a neuroprotective role (Weisman et al 2012). It is interesting to highlight that in the aforementioned pathological conditions an increase in the number of misfolded proteins in the intracellular content it is also produced, a fact that has been related to an impairment of the Ubiquitin-Proteasome System (UPS) (Dantuma & Lindsten 2010). The UPS is the main system responsible for controlling the cellular proteostasis (Kaushik & Cuervo 2015), degrading in a specific and selective manner the majority of intracellular proteins (Hershko & Ciechanover 1998)...
Nucleotides, which act as neurotransmitters in the Central Nervous System (CNS), are involved in several physiological and pathological processes (Burnstock 2007). This role as neurotransmitters is due to their capacity to activate different specifics receptors in the cellular membrane denominated P2 purinergic receptors,. These receptors are divided into two groups: ionotropic receptors (P2X1-7) and metabotropic receptors (P2Y1,2,4,6,11-14) (Burnstock et al 2012). Metabotropic P2Y receptors are expressed in the different cellular lineages that form the CNS where they regulate a wide variety of physiological processes such as cell proliferation, growth or survival (Khakh & Burnstock 2009). Within P2Y receptors, the P2Y2 receptor has special structural characteristics that allow it to interact with both integrins and others receptors, which are related to several physiological and pathological phenomenon (Weisman et al 2012). Hence, it has been described that under neuroinflammation conditions, oxidative stress and neurodegenerative disorders, P2Y2 receptor may play a neuroprotective role (Weisman et al 2012). It is interesting to highlight that in the aforementioned pathological conditions an increase in the number of misfolded proteins in the intracellular content it is also produced, a fact that has been related to an impairment of the Ubiquitin-Proteasome System (UPS) (Dantuma & Lindsten 2010). The UPS is the main system responsible for controlling the cellular proteostasis (Kaushik & Cuervo 2015), degrading in a specific and selective manner the majority of intracellular proteins (Hershko & Ciechanover 1998)...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Veterinaria, Departamento de Bioquímica y Biología Molecular IV, leída el 24-05-2017