CO4: Neurodegeneration and Neuroreparation

The primary objective of the research group is the multidisciplinary approach to the study of the molecular, cellular and synaptic mechanisms underlying 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 applicable to various neurological conditions that involve neuronal degeneration and/or synaptic alterations. For this purpose, the group has several cellular 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 whole organism. By means of pharmacological and genetic tools we can identify and validate at preclinical level new therapeutic strategies for their subsequent translation to the patient. The group also aims to develop and validate protocols for the determination of biomarkers with clinical validity.

• Neuronal vulnerability. Cellular and molecular mechanisms involved in the sensitization of neurons to degeneration.
• Intrinsic neuronal excitability. Ionic channels and modulating agents of active and passive neuronal membrane properties.
• Motor physiopathologies. 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 synapses. 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 translational potential to the clinic.
• Identification and development of new tools that delay neuronal degeneration and/or repair damaged nerve tissue.
• Development and validation of new protocols for the determination of biomarkers in neurological and psychiatric diseases.

• Responsible Researchers:
  • Bernardo Moreno López (PI).
  • David González Forero (Co-IR).
• Researchers:
  • 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.

• Ministry of Economy and Business. BFU2015-71422-R. IP: Bernardo Moreno López: Role of membrane-derived phospholipids in synaptic plasticity and regulation of neuronal excitability. Involvement in neuronal death in a model of ALS.
• Carlos III Health Institute. PI11/00013. PI: David González-Forero. Role of the imbalance in activity between NR2 subunits of the NMDA-like receptor in the loss of synaptic inputs and death of neonatal motor neurons after axonal injury.
• Ministry of Science and Innovation. SAF2011-23633 IP: Bernardo Moreno López: Mechanisms that sensitize motor neurons to death: the case of altered TASK-1 expression by deregulation of the transcription factor SP.

• Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía. P11/CTS/7281 PI: Bernardo Moreno López. Mechanisms that sensitize motor neurons to death: the case of the alteration of TASK-1 expression by deregulation of the transcription factor 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 progression 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 POSITION THAT THE JOURNAL OCCURS IN THE CATEGORY MULTIDISCIPLINARY SCIENCES: 5 out of 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 POSITION THAT THE JOURNAL OCCURS IN THE BIOLOGY CATEGORY: 22 out of 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 POSITION THAT THE JOURNAL OCCURS IN THE BIOCHEMISTRY AND MOLECULAR BIOLOGY CATEGORY: 90 out of 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 POSITION THAT THE JOURNAL OCCURS IN THE BIOLOGY CATEGORY: 2 of 86, D1 Paper highlighted by 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 RATIO: 5.008 REVIEW POSITION IN ONCOLOGY CATEGORY: 36 out of 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 POSITION THAT THE JOURNAL OCCUPIES IN THE ONCOLOGY CATEGORY: 36 of 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 POSITION THAT THE JOURNAL OCCURS IN THE CATEGORY PHARMACOLOGY: 19 of 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 RATIO: 3.362. REVIEW POSITION IN ONCOLOGY CATEGORY: 81 out of 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 POSITION THAT THE JOURNAL OCCURS IN THE NEUROSCIENCE CATEGORY: 96 out of 252, Q2.