Regulación del sistema ubiquitina-proteasoma por los receptores purinérgicos en el sistema nervioso central

Abstract

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) ...