Targeting the Recently Deorphanized Receptor GPR83 for the Treatment of Immunological, Neuroendocrine and Neuropsychiatric Disorders

Lindsay M. Lueptow, Lakshmi A. Devi, Amanda K. Fakira

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

8 Scopus citations


G-protein coupled receptors (GPCRs) are a superfamily of receptors responsible for initiation of a myriad of intracellular signaling cascades. Currently, GPCRs represent approximately 34% of marketed pharmaceuticals, a large portion of which have no known endogenous ligand. These orphan GPCRs represent a large pool of novel targets for drug development. Very recently, the neuropeptide PEN, derived from the proteolytic processing of the precursor proSAAS, has been identified as a selective, high-affinity endogenous ligand for the orphan receptor, GPR83. GPR83 is highly expressed in the brain, spleen and thymus, indicating that this receptor may be a target to treat neurological and immune disorders. In the brain GPR83 is expressed in regions involved in the reward pathway, stress/anxiety responses, learning and memory and metabolism. However, the cell type specific expression of GPR83 in these regions has only recently begun to be characterized. In the immune system, GPR83 expression is regulated by Foxp3 in T-regulatory cells that are involved in autoimmune responses. Moreover, in the brain this receptor is regulated by interactions with other GPCRs, such as the recently deorphanized receptor, GPR171, and other hypothalamic receptors such as MC4R and GHSR. The following review will summarize the properties of GPR83 and highlight its known and potential significance in health and disease, as well as its promise as a novel target for drug development.

Original languageEnglish
Title of host publicationProgress in Molecular Biology and Translational Science
EditorsDavid B. Teplow
PublisherElsevier B.V.
Number of pages25
ISBN (Print)9780128162354
StatePublished - 2018

Publication series

NameProgress in Molecular Biology and Translational Science
ISSN (Print)1877-1173
ISSN (Electronic)1878-0814


  • GPCRs
  • GPR83
  • Immune function
  • Metabolism
  • PEN
  • ProSAAS
  • Reward
  • Stress and anxiety


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