Regulators of G-protein signalling as new central nervous system drug targets.
G-protein-coupled receptors (GPCRs) are major targets for drug discovery. The regulator of G-protein signalling (RGS)-protein family has important roles in GPCR signal transduction. RGS proteins contain a conserved RGS-box, which is often accompanied by other signalling regulatory elements. RGS proteins accelerate the deactivation of G proteins to reduce GPCR signalling; however, some also have an effector function and transmit signals. Combining GPCR agonists with RGS inhibitors should potentiate responses, and could markedly increase the agonist's regional specificity. The diversity of RGS proteins with highly localized and dynamically regulated distributions in brain makes them attractive targets for pharmacotherapy of central nervous system disorders.
Neubig
Richard R
RR
Departments of Pharmacology and Internal Medicine (Hypertension Division), University of Michigan, Ann Arbor, Massachusetts 48109-0632, USA. RNeubig@umich.edu
Siderovski
David P
DP
D000818:Animals; D002491:Central Nervous System Agents / Q000737:chemistry / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006706:Homeostasis; D008958:Models, Molecular; D011487:Protein Conformation; D020710:RGS Proteins / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction
D002491:Central Nervous System Agents; D020710:RGS Proteins; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins