Heteromerization of G protein-coupled receptors: relevance to neurological disorders and neurotherapeutics

CNS Neurol Disord Drug Targets. 2010 Nov;9(5):636-50. doi: 10.2174/187152710793361586.

Abstract

Because G protein-coupled receptors (GPCRs) are numerous, widely expressed and involved in major physiological responses, they represent a relevant therapeutic target for drug discovery, particularly regarding pharmacological treatments of neurological disorders. Among the biological phenomena regulating receptor function, GPCR heteromerization is an important emerging area of interest and investigation. There is increasing evidence showing that heteromerization contributes to the pharmacological heterogeneity of GPCRs by modulating receptor ontogeny, activation and recycling. Although in many cases the physiological relevance of receptor heteromerization has not been fully established, the unique pharmacological and functional properties of heteromers are likely to lead to new strategies in clinical medicine. This review describes the main GPCR heteromers and their implications for major neurological disorders such as Parkinson's disease, schizophrenia and addiction. A better understanding of molecular mechanisms underlying drug interactions related to the targeting of receptor heteromers could provide more specific and efficient therapeutic agents for the treatment of brain diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Drug Delivery Systems / methods*
  • Drug Discovery / methods*
  • Humans
  • Models, Biological
  • Nervous System Diseases / drug therapy*
  • Nervous System Diseases / metabolism
  • Nervous System Diseases / physiopathology*
  • Protein Multimerization / physiology*
  • Receptor Cross-Talk / physiology
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, G-Protein-Coupled / physiology
  • Signal Transduction / physiology

Substances

  • Receptors, G-Protein-Coupled