Author, as appears in the article.: Busquets O, Ettcheto M, Verdaguer E, Castro-Torres RD, Auladell C, Beas-Zarate C, Folch J, Camins A.

Department: Bioquímica i Biotecnologia

URV's Author/s: Folch Lopez, Jaume

Keywords: Neurodegeneration Licochalcone a Kainic acid Hippocampus Epilepsy licochalcone a kainic acid hippocampus epilepsy

Abstract: The mitogen-activated protein kinase family (MAPK) is an important group of enzymes involved in cellular responses to diverse external stimuli. One of the members of this family is the c-Jun-N-terminal kinase (JNK). The activation of the JNK pathway has been largely associated with the pathogenesis that occurs in epilepsy and neurodegeneration. Kainic acid (KA) administration in rodents is an experimental approach that induces status epilepticus (SE) and replicates many of the phenomenological features of human temporal lobe epilepsy (TLE). Recent studies in our group have evidenced that the absence of the JNK1 gene has neuroprotective effects against the damage induced by KA, as it occurs with the absence of JNK3. The aim of the present study was to analyse whether the pharmacological inhibition of JNK1 by Licochalcone A (Lic-A) had similar effects and if it may be considered as a new molecule for the treatment of SE. In order to achieve this objective, animals were pre-treated with Lic-A and posteriorly administered with KA as a model for TLE. In addition, a comparative study with KA was performed between wild type pre-treated with Lic-A and single knock-out transgenic mice for the Jnk1 −/− gene. Our results showed that JNK1 inhibition by Lic-A, previous to KA administration, caused a reduction in the convulsive pattern. Furthermore, it reduced phosphorylation levels of the JNK, as well as its activity. In addition, Lic-A prevented hippocampal neuronal degeneration, increased pro-survival anti-apoptotic mechanisms, reduced pro-apoptotic biomarkers, decreased cellular stress and neuroinflammatory processes. Thus, our results suggest that inhibition of the JNK1 by Lic-A has neuroprotective effects and that; it could be a new potential approach for the treatment of SE and neurodegeneration.

Thematic Areas: Química Psicología Pharmacology & pharmacy Pharmacology Odontología Nutrição Neurosciences Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar General medicine Farmacia Engenharias iv Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cellular and molecular neuroscience Biotecnología Biodiversidade Astronomia / física

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 00283908

Author's mail: jaume.folch@urv.cat

Author identifier: 0000-0002-5051-8858

Record's date: 2023-02-18

Papper version: info:eu-repo/semantics/acceptedVersion

Link to the original source: https://www.sciencedirect.com/science/article/abs/pii/S0028390817304975?via%3Dihub

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Neuropharmacology. 131 440-452

APA: Busquets O, Ettcheto M, Verdaguer E, Castro-Torres RD, Auladell C, Beas-Zarate C, Folch J, Camins A. (2018). JNK1 inhibition by Licochalcone A leads to neuronal protection against excitotoxic insults derived of kainic acid. Neuropharmacology, 131(), 440-452. DOI: 10.1016/j.neuropharm.2017.10.030

Article's DOI: 10.1016/j.neuropharm.2017.10.030

Entity: Universitat Rovira i Virgili

Journal publication year: 2018

Publication Type: Journal Publications