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

被引：90

作者：

Charych, Erik I. ^{[1
]}

Liu, Feng ^{[1
]}

Moss, Stephen J. ^{[2
,3
]}

Brandon, Nicholas J. ^{[1
]}

机构：

[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

来源：

NEUROPHARMACOLOGY | 2009年 / 57卷 / 5-6期

关键词：

Schizophrenia; Psychiatric disorders; Bipolar disorder; GABA; GABA(A) receptor; Prefrontal cortex; GABA(A) receptor associated protein; GAMMA-AMINOBUTYRIC-ACID; HUNTINGTIN-ASSOCIATED PROTEIN-1; NEUROACTIVE STEROID ALLOPREGNANOLONE; DORSOLATERAL PREFRONTAL CORTEX; MESSENGER-RNA EXPRESSION; COIL DOMAIN PROTEINS; SUBUNIT GENE LOCUS; A RECEPTOR; PREGNENOLONE SULFATE; BIPOLAR DISORDER;

D O I：

10.1016/j.neuropharm.2009.07.027

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

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.

引用

页码：481 / 495

页数：15

共 254 条

[1] Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample [J].

Agrawal, Arpana ;

Edenberg, Howard J. ;

Foroud, Tatiana ;

Bierut, Laura J. ;

Dunne, Gerald ;

Hinrichs, Anthony L. ;

Nurnberger, John I. ;

Crowe, Raymond ;

Kuperman, Samuel ;

Schuckit, Marc A. ;

Begleiter, Henri ;

Porjesz, Bernice ;

Dick, Danielle M. .

BEHAVIOR GENETICS, 2006, 36 (05) :640-650

[2] GENE-EXPRESSION FOR GLUTAMIC-ACID DECARBOXYLASE IS REDUCED WITHOUT LOSS OF NEURONS IN PREFRONTAL CORTEX OF SCHIZOPHRENICS [J].

AKBARIAN, S ;

KIM, JJ ;

POTKIN, SG ;

HAGMAN, JO ;

TAFAZZOLI, A ;

BUNNEY, WE ;

JONES, EG .

ARCHIVES OF GENERAL PSYCHIATRY, 1995, 52 (04) :258-266

[3] The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms? [J].

Akwa, Y ;

Ladurelle, N ;

Covey, DF ;

Baulieu, EE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :14033-14037

[4] γ-Syntrophin scaffolding is spatially and functionally distinct from that of the α/β syntrophins [J].

Alessi, Amy ;

Bragg, April D. ;

Percival, Justin M. ;

Yoo, Jean ;

Albrecht, Douglas E. ;

Froehner, Stanley C. ;

Adams, Marvin E. .

EXPERIMENTAL CELL RESEARCH, 2006, 312 (16) :3084-3095

[5] Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database [J].

Allen, Nicole C. ;

Bagade, Sachin ;

McQueen, Matthew B. ;

Ioannidis, John P. A. ;

Kavvoura, Fotini K. ;

Khoury, Muin J. ;

Tanzi, Rudolph E. ;

Bertram, Lars .

NATURE GENETICS, 2008, 40 (07) :827-834

[6] GABA(A) RECEPTOR NEEDS 2 HOMOLOGOUS DOMAINS OF THE BETA-SUBUNIT FOR ACTIVATION BY GABA BUT NOT BY PENTOBARBITAL [J].

AMIN, J ;

WEISS, DS .

NATURE, 1993, 366 (6455) :565-569

[7] Brain function in Duchenne muscular dystrophy [J].

Anderson, JL ;

Head, SI ;

Rae, C ;

Morley, JW .

BRAIN, 2002, 125 :4-13

[8]

Arancibia-Carcamo I. Lorena, 2006, V43, P25, DOI 10.1007/017

[9] GABAA/Benzodiazepine receptor binding in patients with schizophrenia using [11C]Ro15-4513, a radioligand with relatively high affinity for α5 subunit [J].

Asai, Yoshiyuki ;

Takano, Akihiro ;

Ito, Hiroshi ;

Okubo, Yoshiro ;

Matsuura, Masato ;

Otsuka, Akihiko ;

Takahashi, Hidehiko ;

Ando, Tomomichi ;

Ito, Shigeo ;

Arakawa, Ryosuke ;

Asai, Kunihiko ;

Suhara, Tetsuya .

SCHIZOPHRENIA RESEARCH, 2008, 99 (1-3) :333-340

[10] GABAA receptor subtype-selective efficacy:: TPA023, an α2/α3 selective non-sedating anxiolytic and α5IA, an α5 selective cognition enhancer [J].

Atack, John R. .

CNS NEUROSCIENCE & THERAPEUTICS, 2008, 14 (01) :25-35

← 1 2 3 4 5 6 7 8 9 10 →