title: Regulator of G-protein Signaling (RGS)1 and RGS10 Proteins as Potential Drug Targets for Neuroinflammatory and Neurodegenerative Diseases.
abstract: Regulator of G-protein signaling (RGS) proteins were originally identified as negative regulators of G-protein-coupled receptor (GPCR) signaling via their GTPase-accelerating protein (GAP) activity. All RGS proteins contain evolutionarily conserved RGS domain; however, they differ in their size and regulatory domains. RGS1 and RGS10 are smaller than other RGS proteins, and their functions involve various inflammatory responses including autoimmune responses in both the periphery and the central nervous system (CNS). Neuroinflammation is the chronic inflammatory response in the CNS. Acute inflammatory response in the CNS is believed to be beneficial by involving the neuroprotective actions of immune cells in the brain, particularly microglia, to limit tissue damage and to aid in neuronal repair. However, chronically elevated levels of cytokines serve to maintain activation of abundant numbers of immune cells potentiating prolonged inflammatory responses and creating an environment of oxidative stress, which further hastens oxidative damage of neurons. In this review, we describe the implications and features of RGS proteins (specifically RGS1 and RGS10) in neuroinflammation and neurodegenerative diseases. We will discuss the experimental and epidemiological evidence on the benefits of anti-inflammatory interventions by targeting RGS1 and/or RGS10 protein function or expression in order to delay or attenuate the progression of neurodegeneration, particularly in multiple sclerosis (MS) and Parkinson's disease (PD).
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, 501 D. W. Brooks Dr., Athens, Georgia, 30602, USA. jamlee@uga.edu.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, 501 D. W. Brooks Dr., Athens, Georgia, 30602, USA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Bou Dagher
mesh_terms: D016207:Cytokines / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000276:immunology; D009474:Neurons / Q000378:metabolism; D020710:RGS Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D020710:RGS Proteins
keywords: G-protein-coupled receptor (GPCR); Parkinson’s disease; multiple sclerosis; neuroinflammation; regulator of G-protein signaling