Resumen del trabajo presentado al 1st PhD Research Symposium in Health Sciences and Biomedicine, celebrado en la Universidad Autónoma de Madrid el 18 de mayo de 2018.Peer reviewe

Campanero, Miguel R.

Ferrer, Isidro

Fielitz, Jens

Gamir-Morralla, Andrea

García-Guerra, Lucía

Hernández Álvarez, Félix

Iglesias, Teresa

Jurado-Arjona, Jerónimo

León-Reyes, Noelia S. de

Martín-Muñóz, A.

Pose-Utrilla, Julia

Puerto, Ana del

Sebastián-Serrano, Álvaro

Digital.CSIC

www.ibjournals.com 68 2018 | Volume 1 | S. Issue 2 | e000027The role of PKD1 in brain injury: ROS detoxification and neuroprotection.J Pose-Utrilla1,2, L García-Guerra1,2, A Del Puerto1,2, A Martín-Muñóz4, J Jurado-Arjona3,2 , N S De León-Reyes1, A Gamir-Morralla1,2, A Sebastián-Serrano1,2,J Fielitz5,6, I Ferrer7,2, F Hernández3,2, J Ávila3,2, M R Campanero1,8, T Iglesias1,2*1Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain2CIBERNED, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid,Spain3Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Madrid, Spain4Experimental Molecular Imaging, (Molecular Imaging Unit), CIC biomaGUNE,San Sebastian, Spain.5Experimental and Clinical Research Center (ECRC), Charité-Universitätsmedizin, Max-Delbrück-Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany.6Department of Cardiology, Heart Center Brandenburg and Medical University Brandenburg (MHB), Brandenburg, Germany7Instituto de Neuropatología, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain8CIBERCV, Centro de InvestigaciónBiomédica en Red de EnfermedadesCardiovasculares, Instituto de Salud Carlos III, Madrid, Spain*Corresponding author:Teresa Iglesias. Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Madrid, SpainCIBERNED, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, SpainE-mail: tiglesias@iib.uam.esKeywords: Excitotoxicity, oxidative stress, neuronal death, stroke, PKD1Published May 18, 2018.Copyright: © 2018 Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Editor: Name of the editor here.Cite as: J Pose-Utrilla, L García-Guerra, A Del Puerto, A Martín-Muñóz, J Jurado-Arjona, N S De León-Reyes, A Gamir-Morralla, A Sebastián-Serrano, J Fielitz, I Ferrer, F Hernández, J Ávila MR. Campanero, T Iglesias. The role of PKD1 in brain injury: ROS detoxification and neuroprotection. IBJ Plus 2018 (S2):e00027 doi: 10.24217/2531-0151.18v1s2.00027.Funding: Funding explanation.Competing Interests: Competing interest explanation.Introduction: Oxidative stress is a major pathophysiological mediator of degenerative processes in many neurodegenerative diseases. It is an early event produced during excitotoxicity and is one of the main causes of neuronal damage. It has been described that Protein Kinase D1 (PKD1) is activated by oxidative stress and regulate detoxification of free radicals in tumor cells. However, the role of PKD1 in brain injury associated with excitotoxicity and oxidative stress damage has not yet been explored.Methods: We analyze the activity of PKD1 using in vitro and in vivo models of neuronal damage, as well as human ischemic stroke samples. In addition, and through the use of pharmacological inhibitors, lentiviral silencing and neuronal conditional knockout mice we study the role of this kinase in the pro-survival oxidative stress detoxification pathway and the regulation of their activity in these processes.Results: We find that excitotoxicity provokes an inactivation of neuronal PKD1 and as a consequence there is a decline of IKK/NF-κB survival cascade and an increase in reactive oxygen species. We identify the first molecular mechanism involved in PKD1 inactivation, caused in excitotoxicity by the action of phosphatases not identified so far. Consistent with these results, we demonstrate that the elimination of PKD1 in murine models increases neuronal damage after ischemic stroke and the neurospecific expression of dephosphorylation-resistant active PKD1 prevents kainic acid-induced neuronal death in vitro and in vivo.Conclusions: Our data support that the loss of neuronal PKD1 activity is detrimental for neuronal survival and ROS-detoxification and suggest that this kinase could be a promising target for treatment of excitotoxic brain damage associated to acute and chronic neurodegeneration.BIO 27PhD Programme in Molecular Biosciences

The role of PKD1 in brain injury: ROS detoxification and neuroprotection

The role of PKD1 in brain injury: ROS detoxification and neuroprotection

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