Regulators of G-protein signalling as new central nervous system drug targets

Nat Rev Drug Discov. 2002 Mar;1(3):187-97. doi: 10.1038/nrd747.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Central Nervous System Agents / chemistry
  • Central Nervous System Agents / pharmacology*
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / physiology*
  • Homeostasis
  • Models, Molecular
  • Protein Conformation
  • RGS Proteins / chemistry
  • RGS Proteins / metabolism
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / physiology
  • Signal Transduction


  • Central Nervous System Agents
  • RGS Proteins
  • Receptors, Cell Surface
  • GTP-Binding Proteins