c-Jun N-terminal kinases (JNKs) in myocardial and cerebral ischemia/reperfusion injury
- 1RASA Center in Tomsk, Tomsk Polytechnic University, Russia
- 2Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, United States
- 3Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Russia
- 4RASA Center, Kazan Federal University, Russia
- 5Department of Microbiology and Immunology, Montana State University System, United States
In this article, we review the literature regarding the role of c-Jun N-terminal kinases (JNKs) in cerebral and myocardial ischemia/reperfusion injury. Numerous studies demonstrate that JNK-mediated signaling pathways play an essential role in cerebral and myocardial ischemia/reperfusion injury. JNK-associated mechanisms are involved in preconditioning and postconditioning of the heart and the brain. Literature and own studies suggest that JNK inhibitors may exert cardioprotective and neuroprotective properties. The effects of modulating the JNK-depending pathways in the brain and the heart are reviewed. Cardioprotective and neuroprotective mechanisms of JNK inhibitors are discussed in details including synthetic small molecule inhibitors (AS601245, SP600125, IQ-1S, and SR-3306), ion channel inhibitor GsMTx4, JNK-interacting proteins, inhibitors of mixed-lineage kinase (MLK) and MLK-interacting proteins, inhibitors of glutamate receptors, nitric oxide (NO) donors, and anesthetics. The role of JNKs in ischemia/reperfusion injury of the heart in diabetes mellitus is discussed in the context of comorbidities. According to reviewed literature, JNKs represent promising therapeutic targets for protection of the brain and the heart against ischemic stroke and myocardial infarction, respectively. However, different members of the JNK family exert diverse physiological properties which may not allow for systemic administration of non-specific JNK inhibitors for therapeutic purposes. Currently available candidate JNK inhibitors with high therapeutic potential are identified. Further search for selective JNK3 inhibitors remains an important task.
Keywords: Brain, Heart, C-jun-N-terminal kinase, JNK inhibitor, ischemia-reperfusion injury, stroke.
Received: 28 Jan 2018;
Accepted: 13 Jun 2018.
Edited by:Salvatore Salomone, Università degli Studi di Catania, Italy
Reviewed by:Owen L. Woodman, Baker Heart and Diabetes Institute, Australia
Michele Samaja, Università degli Studi di Milano, Italy
Copyright: © 2018 Shvedova, Anfinogenova, Atochina-Vasserman, Schepetkin and Atochin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: MD, PhD. Dmitriy N. Atochin, Tomsk Polytechnic University, RASA Center in Tomsk, Tomsk, 634050, Russia, email@example.com