Theranostics 2018; 8(16):4535-4551. doi:10.7150/thno.25674 This issue

Review

AMPK: Potential Therapeutic Target for Ischemic Stroke

Shuai Jiang1,2*, Tian Li3*, Ting Ji1*, Wei Yi4, Zhi Yang3, Simeng Wang5, Yang Yang1✉, Chunhu Gu4✉

1. 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
2. Department of Aerospace Medicine, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China
3. Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China
4. Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China
5. Center for Human Nutrition, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
*These authors contributed equally to this work.

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Citation:
Jiang S, Li T, Ji T, Yi W, Yang Z, Wang S, Yang Y, Gu C. AMPK: Potential Therapeutic Target for Ischemic Stroke. Theranostics 2018; 8(16):4535-4551. doi:10.7150/thno.25674. Available from https://www.thno.org/v08p4535.htm

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Abstract

Graphic abstract

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.

Keywords: 5'-AMP-activated protein kinase, Ischemic stroke, Metformin, Energy metabolism, Autophagy