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Epigenetic mechanisms, trauma, and psychopathology: targeting chromatin remodeling complexes

机译:表观遗传机制,创伤和精神病理学:靶向染色质重塑复合物

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Environmental pressure affects the genotype throughout different epigenetic processes. There is currently ample evidence on the role of epigenetics in developing various mental disorders. A burden of environmental pressure, such as psychological trauma, and its influence on genotype can lead to a variety of psychopathologies. Thus, this study focuses on the epigenetic activity of the complex protein machinery operating on chromatin – the ATP-dependent chromatin remodeling complexes. Although there are several recent studies on the molecular structure, functions, and taxonomy of ATP-dependent chromatin remodeling complexes, the focus of this paper is to highlight the importance of those ‘protein machines’ in developing psychiatric disorders. Data were obtained from human preclinical and clinical studies. The results of this review indicate an importance of ATP-dependent chromatin remodeling complexes in the interaction between environmental factors, including traumatic events, and genetic vulnerability to stress. Several studies indicate that ATP-dependent chromatin remodeling complexes play a crucial role in the development and consolidation of memory, in neurodevelopmental processes, and in etiology depressive-like behavior. Thus, the activity of those ‘protein machines’ emerges as a key factor in the pathophysiology of various psychiatric diseases. It can also be concluded that the limitations of clinical studies may be explained by inappropriate laboratory methods and research paradigms due to the delayed timeframe of biochemical responses to environmental stimuli. Future research in this field may enable a better understanding of the pathophysiology of psychiatric diseases and contribute to the development of novel molecular treatment targets.
机译:环境压力影响在不同的外延遗传过程中的基因型。目前有充分的证据表明表观生物学在发展各种精神障碍方面的作用。环境压力的负担,如心理创伤,对基因型的影响可能导致各种各样的精神病理学。因此,该研究侧重于在染色质上运行的复杂蛋白机械的表观遗传活性 - ATP依赖性染色质重塑复合物。尽管有几个关于ATP依赖性染色质重塑复合物的分子结构,功能和分类的研究,但本文的重点是突出这些蛋白质机器在开发精神病疾病方面的重要性。数据是从人临床前和临床研究获得的。本综述结果表明ATP依赖性染色质改造复合物在环境因子之间的相互作用中的重要性,包括创伤事件和遗传脆性对应激的遗传脆弱性。几项研究表明,ATP依赖性染色质重塑复合物在内核开发过程和病因抑郁的行为中发挥着记忆的开发和整合中的至关重要作用。因此,这些“蛋白质机器”的活性出现为各种精神疾病病理生理学中的关键因素。还可以得出结论,临床研究的局限性可以通过不适当的实验方法和研究范式来解释,由于生化反应对环境刺激的延迟时间框架。该领域的未来研究可以更好地理解精神疾病的病理生理学,并有助于开发新的分子治疗靶标。

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