GABA(A) receptors and their associated proteins: implications in the etiology and treatment of schizophrenia and related disorders.
Gamma-aminobutyric acid type A (GABA(A)) receptors play an important role in mediating fast synaptic inhibition in the brain. They are ubiquitously expressed in the CNS and also represent a major site of action for clinically relevant drugs. Recent technological advances have greatly clarified the molecular and cellular roles played by distinct GABA(A) receptor subunit classes and isoforms in normal brain function. At the same time, postmortem and genetic studies have linked neuropsychiatric disorders including schizophrenia and bipolar disorder with GABAergic neurotransmission and various specific GABA(A) receptor subunits, while evidence implicating GABA(A)R-associated proteins is beginning to emerge. In this review we discuss the mounting genetic, molecular, and cellular evidence pointing toward a role for GABA(A) receptor heterogeneity in both schizophrenia etiology and therapeutic development. Finally, we speculate on the relationship between schizophrenia-related disorders and selected GABA(A) receptor associated proteins, key regulators of GABA(A) receptor trafficking, targeting, clustering, and anchoring that often carry out these functions in a subtype-specific manner.
Charych
Erik I
EI
Wyeth Research, Neuroscience Discovery, Princeton NJ 08852, USA. charyce@wyeth.com
Liu
Feng
F
Moss
Stephen J
SJ
Brandon
Nicholas J
NJ
D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*
D014150:Antipsychotic Agents; D011963:Receptors, GABA-A