GABAA receptors and their associated proteins: Implications in the etiology and treatment of schizophrenia and related disorders

NEUROPHARMACOLOGY

卷:57

Review

Charych, Erik I.¹  Liu, Feng¹  Moss, Stephen J.^2,3  Brandon, Nicholas J.¹ 

[1] Wyeth Res, Neurosci Discovery, Princeton, NJ 08852 USA

[2] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA

[3] UCL, Dept Pharmacol, London WC1E 6BT, England

关键词: Schizophrenia;    Psychiatric disorders;    Bipolar disorder;    GABA;    GABA(A) receptor;    Prefrontal cortex;    GABA(A) receptor associated protein;   

DOI  :  10.1016/j.neuropharm.2009.07.027

来源: Elsevier

【 摘 要 】

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. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

Free