Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. Faculty of Life Sciences, Northwest University, 229 Taibai North Road, Xi'an 710069, China.
Department of Aerospace Medicine, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Theranostics. 2018 Aug 10;8(16):4535-4551. doi: 10.7150/thno.25674. eCollection 2018.
5'-AMP-activated protein kinase (AMPK), a member of the serine/threonine (Ser/Thr) kinase group, is universally distributed in various cells and organs. It is a significant endogenous defensive molecule that responds to harmful stimuli, such as cerebral ischemia, cerebral hemorrhage, and, neurodegenerative diseases (NDD). Cerebral ischemia, which results from insufficient blood flow or the blockage of blood vessels, is a major cause of ischemic stroke. Ischemic stroke has received increased attention due to its '3H' effects, namely high mortality, high morbidity, and high disability. Numerous studies have revealed that activation of AMPK plays a protective role in the brain, whereas its action in ischemic stroke remains elusive and poorly understood. Based on existing evidence, we introduce the basic structure, upstream regulators, and biological roles of AMPK. Second, we analyze the relationship between AMPK and the neurovascular unit (NVU). Third, the actions of AMPK in different phases of ischemia and current therapeutic methods are discussed. Finally, we evaluate existing controversy and provide a detailed analysis, followed by ethical issues, potential directions, and further prospects of AMPK. The information complied here may aid in clinical and basic research of AMPK, which may be a potent drug candidate for ischemic stroke treatment in the future.
5'- 腺苷酸活化蛋白激酶（AMPK）是丝氨酸/苏氨酸（Ser/Thr）激酶家族的成员，广泛分布于各种细胞和器官中。它是一种重要的内源性防御分子，对脑缺血、脑出血和神经退行性疾病（NDD）等有害刺激做出反应。脑缺血是由于血流不足或血管阻塞引起的，是缺血性中风的主要原因。由于其“3H”效应（高死亡率、高发病率和高致残率），缺血性中风受到了越来越多的关注。大量研究表明，AMPK 的激活对大脑具有保护作用，但其在缺血性中风中的作用尚不清楚。基于现有证据，我们介绍了 AMPK 的基本结构、上游调节剂和生物学作用。其次，我们分析了 AMPK 与神经血管单元（NVU）的关系。第三，讨论了 AMPK 在缺血不同阶段的作用和当前的治疗方法。最后，我们评估了现有的争议，并进行了详细的分析，同时探讨了伦理问题、潜在的方向和 AMPK 的进一步前景。这里汇集的信息可能有助于 AMPK 的临床和基础研究，它可能成为未来治疗缺血性中风的潜在药物候选物。
