ΔFosB: a Molecular Switch for Reward
ΔFosB: a Molecular Switch for Reward
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ΔFosB：奖励的分子开关
DOI：
10.4303/jdar/235651
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发表时间：
2013
影响因子：
5.2
通讯作者：
E. Nestler
中科院分区：
文献类型：
--
作者：
E. Nestler
Δ FosB是转录因子Fos家族的成员。虽然所有其他家族成员都是在对大量急性刺激的反应中迅速但短暂地被诱导，但Δ FosB的独特之处在于，由于其不寻常的蛋白质稳定性，它会在重复刺激中积累。在药物成瘾的动物模型中，在大脑的奖励区域内，Δ FosB的这种延长的诱导已经被牵连，大量的证据表明Δ FosB促进奖励和动机，并作为药物致敏和增加药物自我给药的关键机制。这已经在人类死后得到了验证，在成瘾大脑的奖励区域中发现了升高的Δ FosB水平。Δ FosB作为一种转录因子，通过调控特定靶基因的表达而产生这种行为表型。我们正在通过使用候选基因方法以及使用全基因组方法来鉴定Δ FosB的此类转录靶点。最近的工作分析了染色质重塑-药物调节基因中组蛋白和其他核蛋白的翻译后修饰的变化-以描绘Δ FosB在体内调节靶基因表达以介导药物诱导的突触，神经和行为可塑性的详细分子机制。这些对Δ FosB的研究为药物成瘾的分子基础提供了新的见解，这为可能的治疗开发定义了一系列新的靶点。
ΔFosB is a member of the Fos family of transcription factors. While all other family members are induced rapidly but transiently in response to a host of acute stimuli, ΔFosB is unique in that it accumulates in response to repeated stimulation due to its unusual protein stability. Such a prolonged induction of ΔFosB, within the brain's reward regions, has been implicated in animal models of drug addiction, with a wealth of evidence indicating that ΔFosB promotes reward and motivation and serves as a key mechanism of drug sensitization and increased drug self-administration. This has been validated in humans postmortem, with elevated ΔFosB levels seen in reward regions of the addicted brain. As a transcription factor, ΔFosB produces this behavioral phenotype by regulating the expression of specific target genes. We are identifying such transcriptional targets of ΔFosB by use of a candidate gene approach as well as by use of genome-wide methods. Recent work has analyzed chromatin remodeling—changes in the posttranslational modifications of histones and other nuclear proteins at drug-regulated genes— to delineate the detailed molecular mechanisms by which ΔFosB regulates target gene expression in vivo to mediate drug-induced synaptic, neural, and behavioral plasticity. These studies of ΔFosB are providing new insight into the molecular basis of drug addiction, which is defining a host of new targets for possible therapeutic development.
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DOI：
10.1073/pnas.89.13.5764
发表时间：
1992-07-01
影响因子：
11.1
作者：
HOPE, B;KOSOFSKY, B;NESTLER, EJ
通讯作者：
NESTLER, EJ
影响因子：
17.7
作者：
Kalivas, PW;Volkow, ND
通讯作者：
Volkow, ND
影响因子：
3.6
作者：
J. Chen;H. E. Nye;M. Kelz;N. Hiroi;Y. Nakabeppu;B. Hope;E. Nestler
通讯作者：
J. Chen;H. E. Nye;M. Kelz;N. Hiroi;Y. Nakabeppu;B. Hope;E. Nestler
DOI：
10.1073/pnas.87.17.6912
发表时间：
1990-09-01
影响因子：
11.1
作者：
GRAYBIEL, AM;MORATALLA, R;ROBERTSON, HA
通讯作者：
ROBERTSON, HA
可卡因在纹状体和伏隔核中调节慢性 FOS 相关抗原诱导的药理学研究。
DOI：
--
发表时间：
1995
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
--
作者：
Nye,HE;Hope,BT;Kelz,MB;Iadarola,M;Nestler,EJ
通讯作者：
Nestler,EJ