利用点突变小鼠模型微调 AMPK 在生理和疾病中的作用

IF 4 3区 医学 Q2 CELL BIOLOGY Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-08-13 DOI:10.1242/dmm.050798
Naghmana Ashraf, Jeanine L Van Nostrand
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引用次数: 0

摘要

AMP激活蛋白激酶(AMPK)是一种进化保守的丝氨酸/苏氨酸激酶,它能监测细胞的能量状态,使其适应生物体内不断变化的营养和环境条件。AMPK 在细胞生长、自噬和线粒体功能等一系列生理过程中发挥着不可或缺的作用,并与癌症、代谢紊乱、心血管疾病和神经退行性疾病等多种疾病有关。AMPK 通过使多种下游底物磷酸化来协调多种不同的生理结果。然而,为了更好地了解 AMPK 在细胞和代谢平衡中的确切作用,AMPK 在体内介导调节这些底物的重要性仍是一个持续的研究领域。在这里,我们全面概述了我们对 AMPK 体内激酶功能的理解,这是从 AMPK 底物磷酸化突变的小鼠模型中发现的。我们讨论了这些小鼠模型的一些固有局限性,强调了这些研究对了解人类健康和疾病的广泛意义,并探讨了所获得的宝贵见解,这些见解可为未来治疗代谢性和非代谢性疾病的治疗策略提供参考。
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Fine-tuning AMPK in physiology and disease using point-mutant mouse models.

AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that monitors the cellular energy status to adapt it to the fluctuating nutritional and environmental conditions in an organism. AMPK plays an integral part in a wide array of physiological processes, such as cell growth, autophagy and mitochondrial function, and is implicated in diverse diseases, including cancer, metabolic disorders, cardiovascular diseases and neurodegenerative diseases. AMPK orchestrates many different physiological outcomes by phosphorylating a broad range of downstream substrates. However, the importance of AMPK-mediated regulation of these substrates in vivo remains an ongoing area of investigation to better understand its precise role in cellular and metabolic homeostasis. Here, we provide a comprehensive overview of our understanding of the kinase function of AMPK in vivo, as uncovered from mouse models that harbor phosphorylation mutations in AMPK substrates. We discuss some of the inherent limitations of these mouse models, highlight the broader implications of these studies for understanding human health and disease, and explore the valuable insights gained that could inform future therapeutic strategies for the treatment of metabolic and non-metabolic disorders.

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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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