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

Author(s):Show less -

Busquets, Oriol ^{[1, 2, 3, 4]} ; Ettcheto, Miren ^{[1, 2, 3, 4]} ; Cano, Amanda ^{[5, 2, 6]} ; Manzine, Patricia R. ^[7] ; Sanchez-Lopez, Elena ^{[5, 6]} ; Espinosa-Jimenez, Triana ^{[2, 3, 4]} ; Verdaguer, Ester ^{[2, 4, 8]} ; Dario Castro-Torres, Ruben ^{[1, 2, 9, 10, 3, 4, 8]} ; Beas-Zarate, Carlos ^{[9, 10]} ; Sureda, Francesc X. ^{[1, 2]} ; Olloquequi, Jordi ^[11] ; Auladell, Carme ^{[2, 4, 8]} ; Folch, Jaume ^{[1, 2]} ; Camins, Antoni ^{[2, 3, 4, 11]}

Affiliation:Show less -

^[1] Univ Rovira & Virgili, Dept Biochem & Biotechnol, Fac Med & Life Sci, Reus 43201 - Spain

^[2] Inst Salud Carlos III, Biomed Res Networking Ctr Neurodegenerat Dis CIBE, Madrid 28029 - Spain

^[3] Univ Barcelona, Dept Pharmacol Toxicol & Therapeut Chem, Fac Pharm & Food Sci, E-08028 Barcelona - Spain

^[4] Univ Barcelona, Inst Neurosci Neuro UB, E-08028 Barcelona - Spain

^[5] Univ Barcelona, Inst Nanosci & Nanotechnol IN2UB, E-08028 Barcelona - Spain

^[6] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharm Pharmaceut Technol & Phys Chem, E-08028 Barcelona - Spain

^[7] Fed Univ Sao Carlos UFSCar, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil

^[8] Univ Barcelona, Fac Biol, Dept Cellular Biol Physiol & Immunol, E-08028 Barcelona - Spain

^[9] Univ Guadalajara, Dept Cellular & Mol Biol, CUCBA, Guadalajara 45200, Jalisco - Mexico

^[10] Neurosci Div, Guadalajara 45200, Jalisco - Mexico

^[11] Univ Autonoma Chile, Lab Cellular & Mol Pathol, Inst Ciencias Biomed, Fac Ciencias Salud, Talca 3460000 - Chile

• Document type: Review article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 21, n. 1 JAN 1 2020.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 17/13224-5 - Study of the JNK1 pathway as a selective target for the treatment of cognitive metabolic disorder: ADAM10 protein analysis
• Grantee: Patricia Regina Manzine Moralles
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 15/26084-1 - Evaluation of platelet ADAM10 in non-Alzheimer's dementias
• Grantee: Patricia Regina Manzine Moralles
• Support Opportunities: Scholarships in Brazil - Post-Doctoral