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治疗研发中的基因组学

Genomics in Treatment Development.

作者信息

Dwivedi Yogesh, Shelton Richard C

机构信息

Department of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

出版信息

Adv Neurobiol. 2023;30:363-385. doi: 10.1007/978-3-031-21054-9_15.

Abstract

The Human Genome Project mapped the 3 billion base pairs in the human genome, which ushered in a new generation of genomically focused treatment development. While this has been very successful in other areas, neuroscience has been largely devoid of such developments. This is in large part because there are very few neurological or mental health conditions that are related to single-gene variants. While developments in pharmacogenomics have been somewhat successful, the use of genetic information in practice has to do with drug metabolism and adverse reactions. Studies of drug metabolism related to genetic variations are an important part of drug development. However, outside of cancer biology, the actual translation of genomic information into novel therapies has been limited. Epigenetics, which relates in part to the effects of the environment on DNA, is a promising newer area of relevance to CNS disorders. The environment can induce chemical modifications of DNA (e.g., cytosine methylation), which can be induced by the environment and may represent either shorter- or longer-term changes. Given the importance of environmental influences on CNS disorders, epigenetics may identify important treatment targets in the future.

摘要

人类基因组计划绘制了人类基因组中的30亿个碱基对,开创了新一代以基因组为重点的治疗方法开发。虽然这在其他领域非常成功,但神经科学在很大程度上缺乏此类进展。这在很大程度上是因为与单基因变异相关的神经或精神健康状况非常少。虽然药物基因组学的发展取得了一定成功,但遗传信息在实际应用中主要涉及药物代谢和不良反应。与基因变异相关的药物代谢研究是药物开发的重要组成部分。然而,除了癌症生物学领域,基因组信息实际转化为新疗法的情况有限。表观遗传学部分涉及环境对DNA的影响,是一个与中枢神经系统疾病相关的、有前景的新领域。环境可以诱导DNA的化学修饰(例如,胞嘧啶甲基化),这种修饰可由环境诱导,可能代表短期或长期变化。鉴于环境影响对中枢神经系统疾病的重要性,表观遗传学未来可能会确定重要的治疗靶点。

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