Role of c-Jun N-Terminal Kinases (JNKs) in Epilepsy and Metabolic Cognitive Impairment

Int J Mol Sci. 2019 Dec 30;21(1):255. doi: 10.3390/ijms21010255.


Previous studies have reported that the regulatory function of the different c-Jun N-terminal kinases isoforms (JNK1, JNK2, and JNK3) play an essential role in neurological disorders, such as epilepsy and metabolic-cognitive alterations. Accordingly, JNKs have emerged as suitable therapeutic strategies. In fact, it has been demonstrated that some unspecific JNK inhibitors exert antidiabetic and neuroprotective effects, albeit they usually show high toxicity or lack therapeutic value. In this sense, natural specific JNK inhibitors, such as Licochalcone A, are promising candidates. Nonetheless, research on the understanding of the role of each of the JNKs remains mandatory in order to progress on the identification of new selective JNK isoform inhibitors. In the present review, a summary on the current gathered data on the role of JNKs in pathology is presented, as well as a discussion on their potential role in pathologies like epilepsy and metabolic-cognitive injury. Moreover, data on the effects of synthetic small molecule inhibitors that modulate JNK-dependent pathways in the brain and peripheral tissues is reviewed.

Keywords: JNK inhibitor; brain; c-Jun-N-terminal kinase; cognitive impairment; epilepsy; metabolism; type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Cognitive Dysfunction / metabolism*
  • Cognitive Dysfunction / pathology
  • Diabetes Mellitus, Type 2 / metabolism
  • Endoplasmic Reticulum Stress
  • Epilepsy / metabolism*
  • Epilepsy / pathology
  • Humans
  • Hypoglycemic Agents / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / drug effects
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Signaling System / physiology
  • Mitochondria / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Neuroprotective Agents / antagonists & inhibitors
  • Protein Isoforms


  • Hypoglycemic Agents
  • Neuroprotective Agents
  • Protein Isoforms
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases