Protein complexes as psychiatric and neurological drug targets.

ABSTRACT

The need for improved medications for psychiatric and neurological disorders is clear. Difficulties in finding such drugs demands that all strategic means be utilized for their invention. The discovery of forebrain specific AMPA receptor antagonists, which selectively block the specific combinations of principal and auxiliary subunits present in forebrain regions but spare targets in the cerebellum, was recently disclosed. This discovery raised the possibility that other auxiliary protein systems could be utilized to help identify new medicines. Discussion of the TARP-dependent AMPA receptor antagonists has been presented elsewhere. Here we review the diversity of protein complexes of neurotransmitter receptors in the nervous system to highlight the broad range of protein/protein drug targets. We briefly outline the structural basis of protein complexes as drug targets for G-protein-coupled receptors, voltage-gated ion channels, and ligand-gated ion channels. This review highlights heterodimers, subunit-specific receptor constructions, multiple signaling pathways, and auxiliary proteins with an emphasis on the later. We conclude that the use of auxiliary proteins in chemical compound screening could enhance the detection of specific, targeted drug searches and lead to novel and improved medicines for psychiatric and neurological disorders.