Super-conserved receptors expressed in the brain: biology and medicinal chemistry efforts

Future Med Chem. 2022 Jun;14(12):899-913. doi: 10.4155/fmc-2022-0006. Epub 2022 May 10.

Abstract

The super-conserved receptors expressed in the brain (SREB) constitute a family of orphan G protein-coupled receptors that include GPR27 (SREB1), GPR85 (SREB2) and GPR173 (SREB3). Their sequences are highly conserved in vertebrates, and they are almost exclusively expressed in the central nervous system. This family of receptors has attracted much attention due to their putative physiological functions and their potential as novel drug targets. The SREB family has been postulated to play important roles in a wide range of different diseases, including pancreatic β-cell insulin secretion and regulation, schizophrenia, autism and atherosclerosis. This review intends to provide a comprehensive overview of the SREB family and its recent advances in biology and medicinal chemistry.

Keywords: G protein-coupled receptor; GPR173; GPR27; GPR85; SREB family; autism; schizophrenia; super-conserved receptors.

Plain language summary

In recent years, the super-conserved receptors expressed in the brain called GPR27, GPR85 and GPR173 have attracted much interest in the field of medicinal science. They have one important feature in common: they are all almost entirely found in the brain. Researchers have investigated their functions in the body in various animal models, as well as their utility in future drug development. GPR27 has been found to be involved in insulin and blood sugar processes in the body and therefore may be important for diabetes treatment. GPR85 is thought to be linked to brain diseases such as schizophrenia and autism. GPR173 is linked to many different illnesses, including atherosclerosis (the buildup of fats, cholesterol and other substances in arteries) and Type 2 diabetes.

Publication types

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

MeSH terms

  • Animals
  • Biology
  • Brain / metabolism
  • Central Nervous System / metabolism
  • Chemistry, Pharmaceutical*
  • Insulin-Secreting Cells* / metabolism
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • Receptors, G-Protein-Coupled