ATP-Citrate Lyase (ACLY):从分子洞察到治疗意义的广泛研究

Aswathi K Biju, Rahul Raj Chennam Lakshmikumar, Kannan R. R. Rengasamy
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摘要

ATP Citrate Lyase(ACLY)是连接碳水化合物代谢和脂质生物合成的核心酶,对各种生理过程至关重要,并与多种病症有关。这篇综述全面介绍了 ACLY 这种处于脂质生物合成和细胞代谢界面的关键酶。它对多种生理功能起着至关重要的作用,因此是一个极具价值的研究课题。文章从 ACLY 的生物化学和分子生物学入手,阐明了其结构特征、功能和调控机制,尤其是在脂质合成和组蛋白乙酰化方面的作用。考虑到病理生理学方面,该综述还研究了 ACLY 失调与相关疾病之间的关系,从机理上解释了其对病理状况的贡献。对 ACLY 抑制剂的解释如下:概述这些抑制剂,了解其作用机制,分析其有效性和特异性。接下来的章节将从临床前研究(总结主要发现和治疗潜力方面的知识)过渡到临床试验。综述提供了有关 ACLY 研究的最新信息,整合了多种来源的数据,以提供深入的了解。最后,它介绍了开发 ACLY 抑制剂所面临的挑战和前景,考虑了克服这些挑战的策略,以及这一前景广阔的领域未来的研发之路。这项全面的研究不仅概括了目前的知识,还旨在启发和指导未来对 ACLY 这一复杂领域及其作为治疗靶点的潜力的研究,最终改善患者的治疗效果和生活质量。
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ATP-Citrate Lyase (ACLY): An Extensive Investigation from Molecular Insight to Therapeutic implications
ATP Citrate Lyase (ACLY) is a central enzyme bridging carbohydrate metabolism and lipid biosynthesis, crucial for various physiological processes and implicated in numerous pathologies. This review comprehensively describes ACLY, a pivotal enzyme at lipid biosynthesis and cellular metabolism interface. It serves as crucial role for several physiological functions, making it a highly valued topic for research. Starting with a description of the biochemistry and molecular biology of ACLY, elucidating its structural features, functions, and regulatory mechanisms, particularly in lipid synthesis and histone acetylation. Considering the pathophysiological aspect, the review also examines the relationship between ACLY dysregulation and associated diseases, explaining its contribution to pathological conditions mechanistically. An explanation of ACLY inhibitors is as follows: an overview of these inhibitors, an understanding of their mechanisms of action, and an analysis of their effectiveness and specificity. The following sections transition from preclinical studies, summarising key findings and knowledge into therapeutic potential, to clinical trials. The review offers updated information about ACLY research, integrating data from multiple sources to give an in-depth understanding. It concludes with the challenges and outlook facing the developing ACLY inhibitors, considering the strategies to overcome these challenges and the upcoming path in research and development in this promising field. This comprehensive examination not only encapsulates the knowledge at present but also aims to inspire and guide future inquiries into the complex realm of ACLY and its potential as a therapeutic target, ultimately improving patient outcomes and quality of life.
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