Parira Tiyash, Laverde Alejandra, Agudelo Marisela
Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, FL 33199, USA.
J Alcohol Drug Depend. 2017 Apr;5(2). doi: 10.4172/2329-6488.1000259. Epub 2017 Mar 20.
Epigenetic studies have led to a more profound understanding of the mechanisms involved in chronic conditions. In the case of alcohol addiction, according to the National Institute on Alcohol Abuse and Alcoholism, 16 million adults suffer from Alcohol Use Disorders (AUDs). Even though therapeutic interventions like behavioral therapy and medications to prevent relapse are currently available, no robust cure exists, which stems from the lack of understanding the mechanisms of action of alcohol and the lack of development of precision medicine approaches to treat AUDs. Another common group of addictive substance, cannabinoids, have been studied extensively to reveal they work through cannabinoid receptors. Therapeutic applications have been found for the cannabinoids and a deeper understanding of the endocannabinoid system has been gained over the years. Recent reports of cannabinergic mechanisms in AUDs has opened an exciting realm of research that seeks to elucidate the molecular mechanisms of alcohol-induced end organ diseases and hopefully provide insight into new therapeutic strategies for the treatment of AUDs. To date, several epigenetic mechanisms have been associated with alcohol and cannabinoids independently. Therefore, the scope of this review is to compile the most recent literature regarding alcohol and cannabinoids in terms of a possible epigenetic connection between the endocannabinoid system and alcohol effects. First, we will provide an overview of epigenetics, followed by an overview of alcohol and epigenetic mechanisms with an emphasis on histone modifications and DNA methylations. Then, we will provide an overview of cannabinoids and epigenetic mechanisms. Lastly, we will discuss evidence of interactions between alcohol and cannabinergic pathways and possible insights into the novel epigenetic mechanisms underlying alcohol-cannabinergic pathway activity. Finalizing the review will be a discussion of future directions and therapeutic applications.
表观遗传学研究使人们对慢性病所涉及的机制有了更深刻的理解。就酒精成瘾而言，根据美国国立酒精滥用与酒精中毒研究所的数据，1600万成年人患有酒精使用障碍（AUDs）。尽管目前有行为疗法和预防复发的药物等治疗干预措施，但尚无有效的治愈方法，这源于对酒精作用机制的了解不足以及缺乏治疗AUDs的精准医学方法。另一类常见的成瘾物质——大麻素，已被广泛研究，结果表明它们通过大麻素受体发挥作用。多年来，人们已经发现了大麻素的治疗应用，并对内源性大麻素系统有了更深入的了解。最近关于AUDs中大麻素能机制的报道开启了一个令人兴奋的研究领域，该领域旨在阐明酒精引起的终末器官疾病的分子机制，并有望为AUDs的治疗提供新的治疗策略。迄今为止，几种表观遗传机制已分别与酒精和大麻素相关联。因此，本综述的范围是汇编有关酒精和大麻素的最新文献，内容涉及内源性大麻素系统与酒精效应之间可能的表观遗传联系。首先，我们将概述表观遗传学，接着概述酒精和表观遗传机制，重点是组蛋白修饰和DNA甲基化。然后，我们将概述大麻素和表观遗传机制。最后，我们将讨论酒精与大麻素能途径之间相互作用的证据，以及对酒精 - 大麻素能途径活性潜在的新表观遗传机制的可能见解。综述的结尾将是对未来方向和治疗应用的讨论。
