Position: Associate Professor
Ester Verdaguer Cardona
everdaguer (at) ub.edu
Dr. Carme Auladell
Department of Cell Biology, Physiology and Immunology
Faculty of Biology, Av. Diagonal 643
08028 Barcelona (Spain)
cauladell (at) ub.edu
The research of our group is focused in the identification of new therapeutic targets to prevent neuronal degeneration through the study of cellular processes that occurs in neurodegenerative diseases.
The c-Jun N-terminal kinase (JNKs), also known as stress-activated protein kinase (SAPK), is activated in response to wide range of cellular stresses. Aberrant activation of JNK has been implicated in the pathogenesis of different neurodegenerative diseases as Alzheimer and Parkinson. Accordingly, that is why we have focused our study on the function and the mechanisms of JNK pathway.
There are three JNK isoforms (JNK1, JNK2 and JNK3) which mediate a plethora of physiological and pathological functions. However, only few data are available about the individual actions of specific JNK in brain functions. The particular implication of the JNK isoforms, in the apoptotic and inflammatory process is analysed using knockout mice jnk1(-/-), jnk2(-/-) and jnk3(-/-) treated with kainic acid (KA), an analogue of glutamate, that mimics the temporal lobe epilepsy in humans. It has been evidenced that the lack of Jnk1 or Jnk3 has a neuroprotective effect against KA. Highlight, either JNK1 or JNK3 as a promising target to block the brain damage induced by excitability. The aim of the project is to study the different processes in each knockout, such as apoptosi, reticulum stress, autophagy and neurogenesis, in order to identify the mechanisms by which the lack of JNK1 o JNK3 can confer neuroprotection.
In order to avoid deleterious effects of conventional knockouts it has been established conditional knockout mice for mkk4 and mkk7 genes using the Cre-LoxP recombination system, under specific promoters for glial and neuronal cells.
Because of JNKs could be a potential target for preventing neurodegenerative diseases, we are studying the alterations of JNK pathway in post-mortem human brains patients affected with neurodegenerative diseases. These human studies are been carried out in collaboration with the Anatomia Patològica, Institut Hospital del Mar, Barcelona.
· de Lemos L, Junyent F, Camins A, Castro-Torres RD, Folch J, Olloquequi J, Beas-Zarate C., Verdaguer E, Auladell C (2017). Neuroprotective Effects of the Absence of JNK1 or JNK3 Isoforms on Kainic Acid-Induced Temporal Lobe Epilepsy-Like Symptoms. Mol Neurobiol. Jun 29. doi: 10.1007/s12035-017-0669-1.
· Verdaguer E., Brox S., Petrov D., Olloquequi J., Romero R., de Lemos M.L., Camins A., Auladell C. (2015). Vulnerability of calbindin, calretinin and parvalbumin in a transgenic/knock-in APPswe/PS1dE9 mouse model of Alzheimer disease together with disruption of hippocampal neurogenesis. Exp Gerontol. 2015 Sep;69:176-88.
· Ettcheto M., Junyent F., de Lemos L., Pallas M., Folch J., Beas-Zarate C,, Verdaguer E., Gómez-Sintes R., Lucas J.J., Auladell C. Camins A. (2015). Mice Lacking Functional Fas Death Receptors Are Protected from Kainic Acid-Induced Apoptosis in the Hippocampus. Mol Neurobiol. 2015 Aug;52(1):120-9.
· Redondo-Castro E., Romero R., Torres-Espín A., Utrera J., Duque D., Junyent F., Auladell C. (2014). Dithiocarb (N,N-diethyldithiocarbamate, DEDTC) decreases levels of biogenic monoamines in the adult mouse brain. Neuropathol Appl Neurobiol. 2014 Oct;40(6):747-58.
· Junyent F., de Lemos L., Verdaguer E., Pallàs M., Folch J., Beas-Zárate C., Camins A., Auladell C. (2012).Lack of Jun-N-terminal kinase 3 (JNK3) does not protect against neurodegeneration induced by 3-nitropropionic acid. Neuropathol Appl Neurobiol. 2012 Jun;38(4):311-21.