Mechanistic and therapeutic insights into class A GPCR dimers in neuropsychiatric disorders

Class A G protein-coupled receptors (GPCRs) constitute the majority of the clinical GPCR targets and are implicated in a wide range of neuropsychiatric disorders. Dimerization of class A GPCRs often introduces unique modes of allosteric modulation, leading to the reprogramming of the downstream signaling relative to individual protomers. In this review, we highlight the experimental evidence and pharmacological properties of class A GPCR dimers involved in mental disorders. We further elucidate the molecular basis of dimer assembly and activation through a comprehensive structural analysis of currently available class A GPCR dimers. Current strategies and therapeutic potential of dimer-specific targeting are also discussed. Together, these insights provide a framework for understanding class A GPCR dimer function and pave the way for the development of dimer-informed therapeutics.