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靶向表观遗传机制治疗酒精使用障碍(AUD)。

Targeting Epigenetic Mechanisms to Treat Alcohol Use Disorders (AUD).

机构信息

Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Salamanca and Group GIR BMD (Bases Moleculares del Desarrollo), University of Salamanca, Salamanca, Spain.

出版信息

Curr Pharm Des. 2021 Oct 5;27(30):3252-3272. doi: 10.2174/1381612827666210203142539.

Abstract

BACKGROUND

The impact of abusive alcohol consumption on human health is remarkable. According to the World Health Organization (WHO), approximately 3.3 million people die annually because of harmful alcohol consumption (the figure represents around 5.9% of global deaths). Alcohol Use Disorder (AUD) is a chronic disease where individuals exhibit compulsive alcohol drinking and present negative emotional states when they do not drink. In the most severe manifestations of AUD, the individuals lose control over intake despite a decided will to stop drinking. Given the multiple faces and the specific forms of this disease, the term AUD often appears in the plural (AUDs). Since only a few approved pharmacological treatments are available to treat AUD and they do not apply to all individuals or AUD forms, the search for compounds that may help to eliminate the burden of the disease and complement other therapeutical approaches is necessary.

METHODS

This work reviews recent research focused on the involvement of epigenetic mechanisms in the pathophysiology of AUD. Excessive drinking leads to chronic and compulsive consumption that eventually damages the organism. The central nervous system is a key target and is the focus of this study. The search for the genetic and epigenetic mechanisms behind the intricated dysregulation induced by ethanol will aid researchers in establishing new therapy approaches.

CONCLUSION

Recent findings in the field of epigenetics are essential and offer new windows for observation and research. The study of small molecules that inhibit key epienzymes involved in nucleosome architecture dynamics is necessary in order to prove their action and specificity in the laboratory and to test their effectivity and safety in clinical trials with selected patients bearing defined alterations caused by ethanol.

摘要

背景

酗酒对人类健康的影响是显著的。根据世界卫生组织(WHO)的数据,每年约有 330 万人因有害饮酒而死亡(这一数字约占全球死亡人数的 5.9%)。酒精使用障碍(AUD)是一种慢性疾病,患者表现为强迫性饮酒,且在不饮酒时会出现负性情绪。在 AUD 最严重的表现中,尽管患者有戒酒的强烈意愿,但仍无法控制饮酒量。鉴于该病的多种表现形式和具体形式,AUD 一词通常以复数形式出现(AUDs)。由于目前仅有少数经过批准的药物治疗方法可用于治疗 AUD,且这些方法并不适用于所有个体或 AUD 形式,因此有必要寻找可能有助于减轻疾病负担并补充其他治疗方法的化合物。

方法

本研究综述了近年来关于表观遗传机制在 AUD 病理生理学中作用的研究进展。过量饮酒会导致慢性和强迫性饮酒,最终损害机体。中枢神经系统是一个关键靶点,也是本研究的重点。寻找导致乙醇引起的复杂失调的遗传和表观遗传机制将有助于研究人员建立新的治疗方法。

结论

近年来在表观遗传学领域的发现至关重要,为观察和研究提供了新的窗口。有必要研究抑制组蛋白结构动力学中关键表观酶的小分子,以在实验室中证明其作用和特异性,并在选定的具有乙醇引起的特定改变的患者中进行临床试验,以测试其有效性和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7019/8778698/d6047319adfc/CPD-27-3252_F1.jpg

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