Abstract
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 post-conditioning of the heart and the brain. The literature and our 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 detail 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. The further search for selective JNK3 inhibitors remains an important task.
| Original language | English |
|---|---|
| Article number | 715 |
| Journal | Frontiers in Pharmacology |
| Volume | 9 |
| Issue number | JUL |
| DOIs | |
| Publication status | Published - 5 Jul 2018 |
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Keywords
- Brain
- C-Jun-N-terminal kinase
- Heart
- Ischemia/reperfusion injury
- JNK inhibitor
- Stroke
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
Cite this
c-Jun N-terminal kinases (JNKs) in myocardial and cerebral ischemia/reperfusion injury. / Shvedova, Maria; Anfinogenova, Yana; Atochina-Vasserman, Elena N.; Schepetkin, Igor A.; Atochin, Dmitriy N.
In: Frontiers in Pharmacology, Vol. 9, No. JUL, 715, 05.07.2018.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - c-Jun N-terminal kinases (JNKs) in myocardial and cerebral ischemia/reperfusion injury
AU - Shvedova, Maria
AU - Anfinogenova, Yana
AU - Atochina-Vasserman, Elena N.
AU - Schepetkin, Igor A.
AU - Atochin, Dmitriy N.
PY - 2018/7/5
Y1 - 2018/7/5
N2 - 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 post-conditioning of the heart and the brain. The literature and our 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 detail 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. The further search for selective JNK3 inhibitors remains an important task.
AB - 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 post-conditioning of the heart and the brain. The literature and our 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 detail 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. The further search for selective JNK3 inhibitors remains an important task.
KW - Brain
KW - C-Jun-N-terminal kinase
KW - Heart
KW - Ischemia/reperfusion injury
KW - JNK inhibitor
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=85049612144&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049612144&partnerID=8YFLogxK
U2 - 10.3389/fphar.2018.00715
DO - 10.3389/fphar.2018.00715
M3 - Review article
VL - 9
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
SN - 1663-9812
IS - JUL
M1 - 715
ER -