title: Systems Pharmacology Links GPCRs with Retinal Degenerative Disorders.
abstract: In most biological systems, second messengers and their key regulatory and effector proteins form links between multiple cellular signaling pathways. Such signaling nodes can integrate the deleterious effects of genetic aberrations, environmental stressors, or both in complex diseases, leading to cell death by various mechanisms. Here we present a systems (network) pharmacology approach that, together with transcriptomics analyses, was used to identify different G protein-coupled receptors that experimentally protected against cellular stress and death caused by linked signaling mechanisms. We describe the application of this concept to degenerative and diabetic retinopathies in appropriate mouse models as an example. Systems pharmacology also provides an attractive framework for devising strategies to combat complex diseases by using (repurposing) US Food and Drug Administration-approved pharmacological agents.
authors.affiliation: Yueyang Hospital and.|Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106; email: kxp65@case.edu.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D000818:Animals; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D049490:Systems Biology / Q000379:methods; D059467:Transcriptome / Q000235:genetics
chemical_list: D043562:Receptors, G-Protein-Coupled
keywords: blindness; network; pharmacological agents; polypharmacology; retina; systems biology
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