ADRA2B and HTR1A: An Updated Study of the Biogenic Amine Receptors Reveals Novel Conserved Motifs Which Play Key Role in Mental Disorders

Adv Exp Med Biol. 2023:1423:79-99. doi: 10.1007/978-3-031-31978-5_7.

Abstract

Mental disorders are strongly connected with several psychiatric conditions including depression, bipolar disorder, schizophrenia, eating disorder, and suicides. There are many biological conditions and pathways that define these complicated illnesses. For example, eating disorders are complex mental health conditions that require the intervention of geneticists, psychiatrists, and medical experts in order to alleviate their symptoms. A patient with suicidal ideation should first be identified and consequently monitored by a similar team of specialists. Both genetics and epigenetics can shed light on eating disorders and suicides as they are found in the main core of such investigations. In the present study, an analysis has been performed on two specific members of the GPCR family toward drawing conclusions regarding their functionality and implementation in mental disorders. Specifically, evolutionary and structural studies on the adrenoceptor alpha 2b (ADRA2B) and the 5-hydroxytryptamine receptor 1A (HTR1A) have been carried out. Both receptors are classified in the biogenic amine receptors sub-cluster of the GPCRs and have been connected in many studies with mental diseases and malnutrition conditions. The major goal of this study is the investigation of conserved motifs among biogenic amine receptors that play an important role in this family signaling pathway, through an updated evolutionary analysis and the correlation of this information with the structural features of the HTR1A and ADRA2B. Furthermore, the structural comparison of ADRA2B, HTR1A, and other members of GPCRs related to mental disorders is performed.

Keywords: 5-hydroxytryptamine receptors; Biogenic amine receptors; Eating disorders; Evolutionary studies; GPCRs; Homology modeling; Mental disorders; Suicide; a2-adrenoceptor.

MeSH terms

  • Feeding and Eating Disorders / genetics
  • Humans
  • Mental Disorders* / genetics
  • Mental Disorders* / metabolism
  • Receptor, Serotonin, 5-HT1A* / genetics
  • Receptors, Adrenergic, alpha-2
  • Receptors, Biogenic Amine* / genetics
  • Receptors, Biogenic Amine* / metabolism
  • Serotonin
  • Suicidal Ideation

Substances

  • ADRA2B protein, human
  • HTR1A protein, human
  • Receptor, Serotonin, 5-HT1A
  • Receptors, Adrenergic, alpha-2
  • Receptors, Biogenic Amine
  • Serotonin