Molecular neurobiology of addiction: what’s all the (Δ)FosB about?
Molecular neurobiology of addiction: what’s all the (Δ)FosB about?
复制标题
DOI：
10.3109/00952990.2014.933840
复制
发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
J. Ruffle
中科院分区：
文献类型：
--
作者：
J. Ruffle
转录因子ΔFosB在反复药物暴露后在许多脑区上调。这种诱导很可能，至少在一定程度上，对成瘾的潜在机制负责，成瘾是一种失调，基因表达的调节被认为是必不可少的。在这篇综述中，我们描述和讨论了ΔFosB的拟议作用以及最近研究结果的含义。ΔFosB的表达表现出依赖于给药物质的可变性，对不同的药物刺激表现出区域特异性。据了解，该转录因子通过与Jun家族蛋白相互作用并形成激活蛋白-1 （AP-1）复合物而起作用。一旦AP-1复合物形成，大量的分子途径被启动，导致遗传、分子和结构的改变。许多已确定的这些分子变化现在与慢性药物暴露后观察到的生理和行为变化直接相关。此外，ΔFosB诱导被认为是评估成瘾潜在治疗干预措施的生物标志物。
Abstract The transcription factor ΔFosB is upregulated in numerous brain regions following repeated drug exposure. This induction is likely to, at least in part, be responsible for the mechanisms underlying addiction, a disorder in which the regulation of gene expression is thought to be essential. In this review, we describe and discuss the proposed role of ΔFosB as well as the implications of recent findings. The expression of ΔFosB displays variability dependent on the administered substance, showing region-specificity for different drug stimuli. This transcription factor is understood to act via interaction with Jun family proteins and the formation of activator protein-1 (AP-1) complexes. Once AP-1 complexes are formed, a multitude of molecular pathways are initiated, causing genetic, molecular and structural alterations. Many of these molecular changes identified are now directly linked to the physiological and behavioral changes observed following chronic drug exposure. In addition, ΔFosB induction is being considered as a biomarker for the evaluation of potential therapeutic interventions for addiction.