CO4: Neurodegeneration and Neurorepair

The primary objective of the research group is the multidisciplinary approach to the study of the molecular, cellular and synaptic mechanisms that underlie numerous neurodegenerative and psychiatric diseases. The multidisciplinary team of basic and clinical researchers has as its main objective the identification of new predictive, diagnostic and/or prognostic biomarkers, therapeutic targets and possible treatments for application to various neurological conditions that present with neuronal degeneration and/or synaptic alterations. To do this, the group has various cell and animal models of various neuropathologies, mainly motor such as ALS, and the necessary technology to study from the subcellular level of organization to the entire organism. Through pharmacological and genetic tools we can identify and validate at a preclinical level new therapeutic strategies for their subsequent transfer to the patient. The group also intends to prepare and validate biomarker determination protocols with clinical validity.

• Neural vulnerability. Cellular and molecular mechanisms involved in the sensitization of neurons to degenerate.
• Intrinsic neuronal excitability. Ionic channels and modulating agents of the active and passive properties of the neuronal membrane.
• Motor pathophysiology. Molecular and cellular mechanisms involved in motor neuron degeneration, with special interest in the rare disease amyotrophic lateral sclerosis (ALS).
• Physiology, plasticity and pathology of the synapse. Molecular mechanisms involved in the normal functioning of synaptic transmission, in synaptic remodeling induced by activity or injury, and in synaptopathies associated with neurological conditions.
• Identification of new biomarkers in patients with neurodegenerative diseases, with particular interest in motor neuron disease.
• Identification and development of new therapeutic tools at the preclinical level with potential translation to the clinic.
• Identification and development of new tools that delay neuronal degeneration and/or repair damaged nervous tissue.
• Development and validation of new protocols for determining biomarkers in neurological and psychiatric diseases.

Motoneuronas Amyotrophic lateral sclerosis Neurodegenerative diseases Electrophysiology Biomarkers Synapse Synaptopathies

• Principal Investigators:
  • Bernardo Moreno López (PI).
  • David González Forero (Co-PI).
• Investigators:
  • Federico Portillo Pacheco.
  • José Juan Vallo de Castro.
  • Victoria García Morales.
  • Carmen Gómez Gómez.
  • Germán Domínguez Vías.
  • Jorge Carlos Morales Camino.
  • Miguel Ángel Moya Molina.
• Predoctoral Fellows:
  • Ángela Gento Caro.
• Research Support Staff:
  • Esther Vilches Herrando.
  • Isis Gastaldo Jordán.

• Ministerio de Economía y Empresa. BFU2015‐71422‐R. PI: Bernardo Moreno López: Papel de los fosfolípidos derivados de membrana en plasticidad sináptica y regulación de la excitabilidad neuronal. Implicación en muerte neuronal en un modelo de ELA.
• Instituto Salud Carlos III. PI11/00013. PI: David González‐Forero. Papel del desbalance en actividad entre subunidades NR2 del receptor tipo NMDA en la pérdida de entradas sinápticas y muerte de motoneuronas neonatales tras la lesión axonal.
• Ministerio de Ciencia e Innovación. SAF2011‐23633 PI: Bernardo Moreno López: Mecanismos que sensibilizan a las motoneuronas a morir: el caso de la alteración de la expresión de TASK‐1 por desregulación del factor de transcripción SP.

• Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía. P11/CTS/7281 PI: Bernardo Moreno López. Mecanismos que sensibilizan a las motoneuronas a morir: el caso de la alteración de la expresión de TASK‐1 por desregulación del factor de transcripción SP‐1.

1. Gento-Caro, A; Vilches-Herrando, E; Garcia-Morales, V; Portillo, F; Rodriguez-Bey, G; Gonzalez-Forero, D; Moreno-Lopez, B-Interfering with lysophosphatidic acid receptor edg2/lpa(1) signalling slows down disease progression in SOD1-G93A transgenic mice-NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY-2021-47-71004-1018--10.1111/nan.12699 QJCR2020:D1-8,09.
2. Garcia-Morales, V; Gento-Caro, A; Portillo, F; Montero, F; Gonzalez-Forero, D; Moreno-Lopez, B-Lysophosphatidic Acid and Several Neurotransmitters Converge on Rho-Kinase 2 Signaling to Manage Motoneuron Excitability-FRONTIERS IN MOLECULAR NEUROSCIENCE-2021-14---788039-10.3389/fnmol.2021.788039 QJCR2020:Q1-5,639.
3. Gento-Caro, A; Vilches-Herrando, E; Portillo, F; Gonzalez-Forero, D; Moreno-Lopez, B-Targeting autotaxin impacts disease advance in the SOD1-G93A mouse model of amyotrophic lateral sclerosis-BRAIN PATHOLOGY-2021----e13022-10.1111/bpa.13022 QJCR2020:D1-6,508.
4. Estella, A; Canton, ML; Munoz, L; Higueras, IR; Nunez, MR; Aranguren, JT; Zaya, B; Gomez, C; Amaya, R; Martinez, AH; Bernal, MDO; De la Fuente, C; Alados, JC; Garnacho-Montero, J-Vaccinated Patients Admitted in ICU with Severe Pneumonia Due to SARS-CoV-2: A Multicenter Pilot Study-JOURNAL OF PERSONALIZED MEDICINE-2021-11-11--1086-10.3390/jpm11111086 QJCR2020:Q1-4,945.

• - Original Articles:
1. Victoria García Morales; Guillermo Rodríguez Bey; Laura Gómez Pérez; Germán Domínguez Vías; David González Forero; Federico Portillo Pacheco; Ángela Gento Caro; Antonio Campos Caro; Ana Garcera; Rosa María Soler; Bernardo Moreno López. Sp1‐regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1. Nature Communications. In press, 2019. Impact index: 11.878 POSICIÓN QUE OCUPA LA REVISTA EN LA CATEGORÍA CIENCIAS MULTIDISCIPLINARES: 5 de 69, D1.

• - Original Articles:
1. Domínguez‐Vías G, Aretxaga‐Maza G, Prieto I, Luna JD, De Gasparo M, Ramírez‐Sánchez M. Diurnal opposite variation between angiotensinase activities in photo‐neuro‐endocrine tissues of rats. Chronobiol Int. 2017;34(9):1180‐1186. Impact index: 2.643 POSICIÓN QUE OCUPA LA REVISTA EN LA CATEGORÍA BIOLOGIA: 22 de 85, Q1.
2. Domínguez‐Vías G, Segarra AB, Martínez‐Cañamero M, Ramírez‐Sánchez M, Prieto I. Influence of a Virgin Olive Oil versus Butter Plus Cholesterol‐Enriched Diet on Testicular Enzymatic Activities in Adult Male Rats. Int J Mol Sci. 2017 Aug 4;18(8). pii: E1701. doi: 10.3390/ijms18081701. Impact index: 3.687 POSICIÓN QUE OCUPA LA REVISTA EN LA CATEGORÍA BIOQUÍMICA Y BIOLOGIA MOLECULAR: 90 de 293, Q2.

• - Original Articles:
1. V. García‐Morales, F. Montero, D. González‐Forero, G. Rodríguez‐Bey, L. Gómez‐Pérez, M.J. Medialdea‐Wandossell, G. Domínguez‐Vías, J.M. García‐Verdugo, B. Moreno‐López. Membrane‐derived phospholipids control synaptic neurotransmission and plasticity. PLoS Biology 13(5): e1002153, 2015. Impact index: 8.668 POSICIÓN QUE OCUPA LA REVISTA EN LA CATEGORÍA BIOLOGÍA: 2 de 86, D1 Trabajo destacado por Robinson R (2015) One Lipid, Two Synaptic Plasticity Pathways. PLoS Biol 13(5): e1002154. doi:10.1371/journal.pbio.1002154).
2. Cuenca‐López MD, Serrano‐Heras G, Montero JC, Corrales‐Sánchez V, Gomez‐Juarez M, Gascón‐Escribano MJ, Morales JC, Voisin V, Núñez LE, Morís F, Bader GD, Pandiella A, Ocaña A. Antitumor activity of the novel multi‐kinase inhibitor EC‐70124 in triple negative breast cancer. Oncotarget. 2015 Sep 29;6(29):27923‐37. Impact index: 5.008 POSICIÓN QUE OCUPA LA REVISTA EN LA CATEGORÍA ONCOLOGÍA: 36 de 213, Q1.
3. Serrano‐Heras G, Cuenca‐López MD, Montero JC, Corrales‐Sanchez V, Morales JC, Núñez LE, Morís F, Pandiella A, Ocaña A. Phospho‐kinase profile of colorectal tumors guides in the selection of multi‐kinase inhibitors. Oncotarget. 2015 Oct 13;6(31):31272‐83. Impact index: 5.008 POSICIÓN QUE OCUPA LA REVISTA EN LA CATEGORÍA ONCOLOGIA: 36 de 213, Q1.
4. V. García‐Morales, F. Montero, B. Moreno‐López. Cannabinoid agonists rearrange synaptic vesicles at excitatory synapses and depress motoneuron activity in vivo. Neuropharmacology 92:69‐79, 2015. Impact index: 4.936 POSICIÓN QUE OCUPA LA REVISTA EN LA CATEGORÍA FARMACOLOGÍA: 19 de 255, D1.

• - Original Articles:
1. Cuenca‐López MD, Montero JC, Morales JC, Prat A, Pandiella A, Ocana A. Phospho‐kinase profile of triple negative breast cancer and androgen receptor signaling. BMC Cancer. 2014 Apr 30;14:302. Impact index: 3.362 POSICIÓN QUE OCUPA LA REVISTA EN LA CATEGORÍA ONCOLOGÍA: 81 de 210, Q2.
• - Review Articles:
1. González‐Forero, B. Moreno‐López. Retrograde response in axotomized motoneurons: Nitric oxide as a key player in triggering reversion toward a dedifferentiated phenotype. Neuroscience 283: 138‐65, 2014. Impact index: 3.357 POSICIÓN QUE OCUPA LA REVISTA EN LA CATEGORÍA NEUROCIENCIAS: 96 de 252, Q2.