Ron Dorit, Messing Robert O
Ernest Gallo Clinic and Research Center, University of California San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA.
Curr Top Behav Neurosci. 2013;13:87-126. doi: 10.1007/7854_2011_161.
Ethanol's effects on intracellular signaling pathways contribute to acute effects of ethanol as well as to neuroadaptive responses to repeated ethanol exposure. In this chapter we review recent discoveries that demonstrate how ethanol alters signaling pathways involving several receptor tyrosine kinases and intracellular tyrosine and serine-threonine kinases, with consequences for regulation of cell surface receptor function, gene expression, protein translation, neuronal excitability and animal behavior. We also describe recent work that demonstrates a key role for ethanol in regulating the function of scaffolding proteins that organize signaling complexes into functional units. Finally, we review recent exciting studies demonstrating ethanol modulation of DNA and histone modification and the expression of microRNAs, indicating epigenetic mechanisms by which ethanol regulates neuronal gene expression and addictive behaviors.
乙醇对细胞内信号通路的影响既导致了乙醇的急性效应，也促成了对反复乙醇暴露的神经适应性反应。在本章中，我们回顾了近期的发现，这些发现展示了乙醇如何改变涉及多种受体酪氨酸激酶以及细胞内酪氨酸和丝氨酸 - 苏氨酸激酶的信号通路，进而影响细胞表面受体功能、基因表达、蛋白质翻译、神经元兴奋性和动物行为的调节。我们还描述了近期的研究工作，这些研究表明乙醇在调节支架蛋白功能方面发挥着关键作用，支架蛋白可将信号复合物组织成功能单元。最后，我们回顾了近期令人兴奋的研究，这些研究证明了乙醇对DNA和组蛋白修饰以及微小RNA表达的调节作用，表明了乙醇调节神经元基因表达和成瘾行为的表观遗传机制。
