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

• Published in: International journal of molecular sciences Vol. 21; no. 1; p. 255
• Main Authors: Busquets, Oriol, Ettcheto, Miren, Cano, Amanda, R. Manzine, Patricia, Sánchez-Lopez, Elena, Espinosa-Jiménez, Triana, Verdaguer, Ester, Dario Castro-Torres, Rubén, Beas-Zarate, Carlos, X. Sureda, Francesc, Olloquequi, Jordi, Auladell, Carme, Folch, Jaume, Camins, Antoni
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.12.2019; MDPI
• Subjects: Animals; Antidiabetics; Apoptosis; Brain - metabolism; Capital punishment; Cell cycle; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - pathology; Cytokines; Deoxyribonucleic acid; Diabetes Mellitus, Type 2 - metabolism; DNA; Endoplasmic Reticulum Stress; Epilepsy - metabolism; Epilepsy - pathology; Gene expression; Growth factors; Humans; Hypoglycemic Agents - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - drug effects; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; Ligands; Lymphoma; MAP Kinase Signaling System - physiology; Mitochondria; Mitochondria - metabolism; Mitogen-Activated Protein Kinases - metabolism; Neuroprotective Agents - antagonists & inhibitors; Oxidative stress; Phosphorylation; Physiology; Protein Isoforms; Proteins; Radiation; Review; Transcription factors; Tumor necrosis factor-TNF; epilepsy; type 2 diabetes; cognitive impairment; metabolism; brain; JNK inhibitor; c-Jun-N-terminal kinase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.