G protein-coupled receptor systems and their role in cellular senescence

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL(2019)

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摘要
Aging is a complex biological process that is inevitable for nearly all organisms. Aging is the strongest risk factor for development of multiple neurodegenerative disorders, cancer and cardiovascular disorders. Age-related disease conditions are mainly caused by the progressive degradation of the integrity of communication systems within and between organs. This is in part mediated by, i) decreased efficiency of receptor signaling systems and ii) an increasing inability to cope with stress leading to apoptosis and cellular senescence. Cellular senescence is a natural process during embryonic development, more recently it has been shown to be also involved in the development of aging disorders and is now considered one of the major hallmarks of aging. G-protein-coupled receptors (GPCRs) comprise a superfamily of integral membrane receptors that are responsible for cell signaling events involved in nearly every physiological process. Recent advances in the molecular understanding of GPCR signaling complexity have expanded their therapeutic capacity tremendously. Emerging data now suggests the involvement of GPCRs and their associated proteins in the development of cellular senescence. With the proven efficacy of therapeutic GPCR targeting, it is reasonable to now consider GPCRs as potential platforms to control cellular senescence and the consequently, age-related disorders. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
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ADP-ribosylation factor GTPase-activating protein, (Arf-GAP),AT1R blockers, (ARB),Aging,Angiotensin II, (Ang II),Ataxia telangiectasia mutated, (ATM),Cellular senescence,G protein-coupled receptor kinase interacting protein 2 (GIT2),G protein-coupled receptor kinase interacting protein 2, (GIT2),G protein-coupled receptor kinase, (GRK),G protein-coupled receptors (GPCRs),G protein-coupled receptors, (GPCRs),Hutchinson–Gilford progeria syndrome, (HGPS),Lysophosphatidic acid, (LPA),Regulator of G-protein signaling, (RGS),Relaxin family receptor 3, (RXFP3),active state, (R*),angiotensin type 1 receptor, (AT1R),angiotensin type 2 receptor, (AT2R),beta2-adrenergic receptor, (β2AR),cyclin-dependent kinase 2, (CDK2),cyclin-dependent kinase inhibitor 1, (cdkn1A/p21),endothelial cell differentiation gene, (Edg),inactive state, (R),latent semantic indexing, (LSI),mitogen-activated protein kinase, (MAPK),nuclear factor kappa-light-chain-enhancer of activated B cells, (NF- κβ),protein kinases, (PK),purinergic receptors family, (P2Y),renin-angiotensin system, (RAS),retinoblastoma, (RB),senescence associated secretory phenotype, (SASP),stress-induced premature senescence, (SIPS),transcription factor E2F3, (E2F3),transmembrane, (TM),tumor suppressor gene PTEN, (PTEN),tumor suppressor protein 53, (p53),vascular smooth muscle cells, (VSMC),β-Arrestin
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