A new understanding of GHSR1a--independent of ghrelin activation

Growth hormone secretagogue receptor 1a (GHSR1a), a member of the G protein-coupled receptor (GPCR) family, is a functional receptor of ghrelin. The expression levels and activities of GHSR1a are affected by various factors. In past years, it has been found that the ghrelin-GHSR1a system can perform biological functions such as anti-inflammation, anti-apoptosis, and anti-oxidative stress. In addition to mediating the effect of ghrelin, GHSR1a also has abnormally high constitutive activity; that is, it can still transmit intracellular signals without activation of the ghrelin ligand. This constitutive activity affects brain functions, growth and development of the body; therefore, it has profound impacts on neurodegenerative diseases and some other age-related diseases. In addition, GHSR1a can also form homodimers or heterodimers with other GPCRs, affecting the release of neurotransmitters, appetite regulation, cell proliferation and insulin release. Therefore, further understanding of the constitutive activities and dimerization of GHSR1a will enable us to better clarify the characteristics of GHSR1a and provide more therapeutic targets for drug development. Here, we focus on the roles of GHSR1a in various biological functions and provide a comprehensive summary of the current research on GHSR1a to provide broader therapeutic prospects for age-related disease treatment.