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非编码 RNA 在酒精使用障碍中的功能作用、调控机制及治疗学应用。

Functional roles, regulatory mechanisms and theranostics applications of ncRNAs in alcohol use disorder.

机构信息

Department of Pharmacy, Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230000, China.

Department of Pharmacy, Hefei Fourth People's Hospital, Hefei, 230000, China.

出版信息

Int J Biol Sci. 2023 Feb 21;19(4):1316-1335. doi: 10.7150/ijbs.81518. eCollection 2023.

Abstract

Alcohol use disorder (AUD) is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is convoluted and poorly understood. There is considerable evidence demonstrating significant associations between multiple heritable factors and the onset and progression of AUD. In recent years, a substantial body of research conducted by emerging biotechnologies has increasingly highlighted the crucial roles of noncoding RNAs (ncRNAs) in the pathophysiology of mental diseases. As in-depth understanding of ncRNAs and their mechanisms of action, they have emerged as prospective diagnostic indicators and preclinical therapeutic targets for a variety of psychiatric illness, including AUD. Of note, dysregulated expression of ncRNAs such as circRNAs, lncRNAs and miRNAs was routinely found in AUD individuals, and besides, exogenous regulation of partial ncRNAs has also been shown to be effective in ameliorating alcohol preference and excessive alcohol consumption. However, the exact molecular mechanism still remains elusive. Herein, we systematically summarized current knowledge regarding alterations in the expression of certain ncRNAs as well as their-mediated regulatory mechanisms in individuals with AUD. And finally, we detailedly reviewed the potential theranostics applications of gene therapy agents targeting ncRNAs in AUD mice. Overall, a deeper comprehension of functional roles and biological mechanisms of ncRNAs may make significant contributions to the accurate diagnosis and effective treatment of AUD.

摘要

酒精使用障碍(AUD)是全球最普遍的神经心理障碍之一,其发病机制复杂且尚未完全了解。有大量证据表明,多种可遗传因素与 AUD 的发生和进展之间存在显著关联。近年来,新兴生物技术的大量研究越来越强调非编码 RNA(ncRNA)在精神疾病病理生理学中的关键作用。随着对 ncRNA 及其作用机制的深入了解,它们已成为各种精神疾病(包括 AUD)的有前途的诊断指标和临床前治疗靶点。值得注意的是,在 AUD 个体中经常发现 ncRNA(如 circRNAs、lncRNAs 和 miRNAs)的表达失调,并且部分 ncRNA 的外源性调节也已被证明在改善酒精偏好和过度饮酒方面是有效的。然而,确切的分子机制仍不清楚。本文系统总结了目前关于 AUD 个体中某些 ncRNA 的表达变化及其介导的调控机制的相关知识。最后,我们详细回顾了针对 AUD 小鼠的 ncRNA 基因治疗剂的潜在治疗应用。总的来说,深入了解 ncRNA 的功能作用和生物学机制可能会为 AUD 的准确诊断和有效治疗做出重大贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9332/10008696/cb09abbd6a11/ijbsv19p1316g001.jpg

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