LABORATORIOS 

Neurovascular research group

Neurovascular research group

Research

Team

Publications

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Research

The lines of work and research of the group focus on the study of the Neurovascular Unit in physiological (including physiological senile aging) and pathological situations, as well as the evaluation of strategies for its protection and repair.

Dysfunction of the Neurovascular Unit predisposes or aggravates the development of diseases with a high socioeconomic impact, such as acute cerebrovascular accident (stroke), chronic neurodegenerative diseases, particularly Alzheimer’s disease (AD), and tumor progression.

In this sense, we investigate the protection and repair mechanisms of the Neurovascular Unit, looking for appropriate molecules for the treatment of these diseases of great clinical and epidemiological importance, both due to their prevalence, incidence and mortality, as well as the degree of sequelae they generate..

To address our objectives we use experimental models in rodents and anatomical and imaging techniques (Nuclear Magnetic Resonance, NMR) as well as histochemical, biochemical, cell and molecular biology techniques and behavioral assays.

Do you want to collaborate with us?

If you are interested in our lines of research and want to propose a project, a contract or want to develop your research training in our group, contact us.

+34 915 854 714

r.martinez@cajal.csic.es

Lines of investigation

1) Cerebral ischemia

We tested: new molecules for the treatment of ischemic stroke.

We used: a mouse model of ligation of the middle cerebral artery.

We value:

  • MRI infarct volumes
  • Markers that are altered in ischemic stroke using Histochemistry, Immunohistochemistry, Biochemistry and Molecular Biology techniques.
  • Improvement through animal behavior tests.

      These images are from an NMR study. The use of this technique allows us to assess the volume of the cerebral infarction produced by ligating the middle cerebral artery, an experimental stroke model that we use in the evaluation of new molecules for its treatment, as we can see in the image on the right.

      2) Alzheimer´s disease

      We tested: New molecules to slow or stop Alzheimer’s disease.
      We employ:
      A mouse model of the disease, double transgenic for human amyloid precursor protein (APP swe) and presenilin 1 (PSEN1 dE9).
      Sections from Alzheimer’s patients.
      We value:

      • Variation in β-amyloid (Aβ) load.
      • Gliosis, inflammation and neurodegeneration using Histochemistry, Immunohistochemistry, Biochemistry and Molecular Biology techniques.
      • Improvement through animal behavior tests.

      Image taken with a fluorescence microscope. The section is stained with Thioflavin-S to quantify β-amyloid deposits in a model of Alzheimer’s disease, and to assess the effect of new molecules for its treatment.

      These microphotographs show different patterns of neurogliosis and its relationship with beta amyloid plaques in sections from Alzheimer’s disease.

      3) Brain tumors

      We tested: the use of nanoparticles (Nanohyperthermia) to stop tumor progression.
      We used: a murine orthotopic model produced by intracerebral injection of tumor cells
      We value:

      • Tumor volumes by MRI.
      • Tumor markers using Histochemistry, Immunohistochemistry, Biochemistry and Molecular Biology techniques.

      These images are from an NMR study. The use of this technique allows us to assess the volume of a brain tumor produced by transplanting glioblastoma tumor cells into a mouse (host), thus obtaining an appropriate experimental model of glioblastoma intracerebral tumor progression that we use in evaluating new therapies.

      Team

      Ricardo Martínez

      Principal Investigator

      Adolfo Toledano

      Ad Honorem Proffessor

      Julia Serrano

      Postoctoral Researcher

      Patricia Fernández

      Postoctoral Researcher

      Aitana Sánchez

      Student

      Publications 

      Publications of the last years

      • Emelina R. Rodríguez-Ruiz, Raquel Herrero-Labrador, Ana P. Fernández-Fernández, Julia Serrano-Masa,José A. Martínez-Montero, Daniel González-Nieto, Mayuri Hana-Vaish, Mohamed Benchekroun ,Lhassane Ismaili*, José Marco-Contelles and Ricardo Martínez-Murillo*, The Proof-of-Concept of MBA121, a Tacrine–Ferulic AcidHybrid, for Alzheimer’s  Disease Therapy. Internat. J. of Molecular Sciences, 24, 12254, 2023. https://doi.org/10.3390/ijms241512254 

      • Knez, Damijan; Diez-Iriepa, Daniel); Chioua, Mourad; Gottinger, Andrea); Denic, Milica ; Chantegreil, Fabien; Nachon, Florian; Brazzolotto, Xavier); Skrzypczak-Wiercioch, Anna; Meden, Anze; Pislar, Anja; Kos, Janko); Zakelj, Simon; Stojan, Jure; Salat, Kinga; Serrano, Julia; Fernandez, Ana Patricia; Sanchez-Garcia, Aitana; Martinez-Murillo, Ricardo; Binda, Claudia; Lopez-Munoz, Francisco); Gobec, Stanislav); Marco-Contelles, Jose.  8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases. Acata Pharmaceutica Sinca, 13, 2152-2174, 2023. https://doi.org/10.1016/j.apsb.2023.01.013

      • Chamorro, Beatriz; Izquierdo-Bermejo, Sara; Serrano, Julia; Hadjipavlou-Litina, Dimitra; Chioua, Mourad; Lopez-Munoz, Francisco; Marco-Contelles, Jose; Martinez-Murillo, Ricardo; Oset-Gasque, Maria Jesus, Neuroprotective and antioxidant properties of new quinolylnitrones in in vitro and in vivo cerebral ischemia models, Scientific Reports, Volume 13, Issue 1, 2023. DOI: http://dx.doi.org/10.1038/s41598-023-29929-7

      • Garcia-Pena, Pablo; Ramos, Milagros; Lopez, Juan M.; Martinez-Murillo, Ricardo; de Arcas, Guillermo); Gonzalez-Nieto, Daniel), Preclinical examination of early-onset thalamic-cortical seizures after hemispheric stroke. Epilepsia, 2023. https://doi.org/10.1073/pnas.120529710

      • Fernandez-Serra, R ; Martinez-Alonso, E; Alcazar, A; Chioua, M; Marco-Contelles, J; Martinez-Murillo, R; Ramos, M; Guinea, GV; Gonzalez-Nieto, D, Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations. International Journal of Molecular Sciences, 23, 7449, 2022. https://doi.org/10.3390/ijms23137449

      • The use of Silica Microparticles to Improve the Efficiency of Optical Hyperthermia (OH). Casanova-Carvajal, O; Zeinoun, M; Urbano-Bojorge, AL; Bacha, F; Livi, JS; Agudo, E; Vargas, G; Ramos, M; Martinez-Murillo, R; Serrano-Olmedo, JJ. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 22 (10) (2021)
        DOI: 10.3390/ijms22105091

      • Reflections on cerebellar neuropathology in classical scrapie. Toledano-Díaz A, Álvarez MI, Rodríguez JJ, Badiola JJ, Monzón M, Toledano A. BIOMOLECULES Apr 28; 11(5):649 (2021) DOI: 10.3390/biom11050649
      • Synthesis, antioxidant properties and neuroprotection of alpha-phenyl-tert-butylnitrone derived HomoBisNitrones in in vitro and in vivo ischemia models. Chamorro, B; Diez-Iriepa, D; Merás-Sáiz, B; Chioua, M; García-Vieira, D; Iriepa, I; Hadjipavlou-Litina, D; López-Muñoz, F; Martínez-Murillo, R; Gonzàlez-Nieto, D; Israel Fernández, I; Marco-Contelles, J; and Oset-Gasque, MJesús.  SCIENTIFIC REPORTS 10 (1), 2020. DOI: 10.1038/s41598-020-70690-y
      • Biomaterials to Neuroprotect the Stroke Brain: A Large Opportunity for Narrow Time Windows. Gonzalez-Nieto, D; Fernandez-Serra, R; Perez-Rigueiro, J; Panetsos, F Martinez-Murillo, R; Guinea, GV. CELLS 9 (5) (2020). DOI: 10.3390/cells9051074
      • Glial Alterations in Aging and Alzheimer’s disease: A novel basis to understand, prevent and treat the degenerative process. Toledano-Díaz A, Álvarez MI, Toledano A. OBM GERIATRICS 4 (2020). DOI: 10.21926/obm.geriatr.2002117
      • Hippocampal CCR5/RANTES elevations in a rodent model of post-traumatic stress disorder: Maraviroc (a CCR5 Antagonist) increases corticosterone levels and enhances fear memory consolidation. Merino JJ, Muñetón-Gomez V, Muñetón-Gómez C, Pérez-Izquierdo MÁ, Loscertales M, Toledano A.
        BIOMOLECULES FEB 1; 10(2):212 (2020). DOI: 10.3390/biom10020212
      • Synthesis, neuroprotective and antioxidant capacity of PBN-related indanonitrones. Jimenez-Almarza, A; Diez-Iriepa, D; Chioua, M; Chamorro, B; Iriepa, I; Martinez-Murillo, R; Hadjipavlou-Litina, D; Oset-Gasque, MJ and Marco-Contelles, J. May 2019 | BIOORGANIC CHEMISTRY 86, pp.445-451, 2019
        DOI: 10.1016/j.bioorg.2019.01.071
      • Slowdown intracranial glioma progression by optical hyperthermia therapy: study on a CT-2A mouse astrocytoma model. Casanova-Carvajal, O; Urbano-Bojorge, AL; Ramos, M; Serrano-Olmedo, JJ; and Martinez-Murillo, R. NANOTECHNOLOGY 30 (35), 2019. DOI: 10.1088/1361-6528/ab2164
      • Elevated systemic L-Kynurenine/L-Tryptophan ratio andi increased IL-1 beta and Chemokine (CX3CL1, MCP-1) proinflammatory mediators in patients with long-term titanium dental implants. Merino JJ, Cabaña Muñoz ME, Toledano A, Garcimartín A, Benedí, J, Camacho Alonso F, Parmigiani Izquierdo JM.
        J CLIN MED SEP 2; 8(9):1368 (2019). DOI: 10.3390/jcm8091368
      • The long-term algae extract and aminosulphurate supplementation modulates SOD-1 activity and decrease heavymetals levels in patients with long-term dental titanium implants and amalgam fillings restorations. Merino JJ, Parmigiani Izquierdo JM, Toledano A,Cabaña Muñoz ME. ANTIOXIDANTS 2019 APR 16, 8(4):101 (2019). DOI: 10.3390/antiox8040101. 8-4
      • Cortical Reshaping and Functional Recovery Induced by Silk Fibroin Hydrogels-Encapsulated Stem Cells Implanted in Stroke Animals. Fernandez-Garcia, L; Perez-Rigueiro, J; Martinez-Murillo, R ; Panetsos, F; Ramos, M; Guinea, GV; Gonzalez-Nieto, D. FRONTIERS IN CELLULAR NEUROSCIENCE 12 (2018)
        DOI: 10.3389/fncel.2018.00296
      • The APPswe/PS1A246E mutations in an astrocytic cell line leads to increased vulnerability to oxygen and glucose deprivation, Ca2+ dysregulation, and mitochondrial abnormalities. Martin-de-Saavedra, MD; Navarro, E; Moreno-Ortega, AJ; Cunha, MP; Hernansanz-Agustin, P ; Leon, R; Cano-Abad, MF ; Martinez-Ruiz, A; Martinez-Murillo, R; Duchen, MR; Lopez, MG. JOURNAL OF NEUROCHEMISTRY 145 (2), pp.170-182 (2018). DOI: 10.1111/jnc.14293
      • Neuron-Astrocyte Signaling is preserved in the Aging Brain. Gomez-Gonzalo, M ; Martin-Fernandez, M ; Martinez-Murillo, R ; Mederos, S ; Hernandez-Vivanco, A ; Jamison, S ;Fernandez AP ; Serrano, J ; Calero, P ; Futch, HS ; Corpas, R ; Sanfeliu, C ; Perea, G ; Araque, A. GLIA: 65 (4):569-580 (2017). DOI: 10.1002/glia.23112
      • The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease. Serrano, MP ; Herrero-Labrador, R ; Futch, HS ; Serrano, J ; Romero, A ; Fernandez AP ; Samadi, A ; Unzeta, M ; Marco-Contelles, J ; Martinez-Murillo, R. JOURNAL OF PSYCHIATRY & NEUROSCIENCE: 42(1):59-69 (2017). DOI: 10.1503/jpn.150209
      • Defective insulin signaling, mediated by inflammation, connects Obesity to Alzheimer Disease; relevant pharmacological therapies and preventive dietary interventions. Rodriguez-Casado A, Toledano-Díaz A, Toledano A. CURR ALZH RES.; 14(8):894-911 (2017). DOI: 10.2174/1567205014666170316161848
      • In Vitro evaluation of Biocompatibility of Uncoated Thermally reduced graphene and carbon nanotube-loaded PVDF Membranes with adult neural stem cell-Derived neurons and glia. Defterali, C; Verdejo, R; Majeed, S; Boschetti-de-Fierro, A; Mendez-Gomez, HR ; Diaz-Guerra, E; Fierro, D; Buhr, K; Abetz, C; Martinez-Murillo, R ; Vuluga, D; Alexandre, M; Thomassin, JM; Detrembleur, C; Jerome, C; Abetz, V; Lopez-Manchado, MA; Vicario-Abejon, C. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY 4 (2016). DOI: 10.3389/fbioe.2016.00094
      • Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy. Rey-Funes, M; Larrayoz, IM; Fernandez, JC; Contartese, DS; Rolon, F; Inserra, PIF; Martinez-Murillo, R; Lopez-Costa, JJ; Dorfman, VB; Martinez, A; Loidl, CF. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY 310 (11), pp.R1011-R101 (2016). DOI: 10.1152/ajpregu.00266.2015
      • Thermally reduced graphene is a permissive material for neurons and astrocytes and de novo neurogenesis in the adult olfactory bulb in vivo
        Defterali, C; Verdejo, R; Peponi, L; Martin, ED; 4Martinez-Murillo, R ; Lopez-Manchado, MA; Vicario-Abejon, C. BIOMATERIALS 82, pp.84-93 (2016). DOI: 10.1016/j.biomaterials.2015.12.010
      • Long-term dynamics of somatosensory activity in a stroke model of distal middle cerebral artery oclussion. Barrios, JA ; Pisarchyk, L; Fernandez-Garcia, L; Barrio, LC; Ramos, M; Martinez-Murillo, R; Gonzalez-Nieto, D. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 36 (3) , pp.606-620 (2016). DOI: 10.3390/ijms22105091
      • Adrenomedullin Expression in Alzheimer’s Brain. Fernandez AP; Masa, JS ; Guedan, MA ; Futch, HS ; Martinez-Murillo, R. CURRENT ALZHEIMER RESEARCH: 13 (4): 428-438 (2016). DOI: 10.2174/1567205013666160229112725
      • ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer’s disease Therapy. Marco-Contelles J, Unzeta M, Bolea I, Esteban G, Ramsay RR, Romero A, Martinez-Murillo R, Carreiras MC, Ismaili L. FRONT NEUROSCI: 10:294 (2016). DOI: 10.3389/fnins.2016.00294
      • Lack of adrenomedullin in mouse endothelial cells results in defective angiogenesis, enhanced vascular permeability, less metastasis, and more brain damage. Ochoa-Callejero L, Pozo-Rodrigalvarez A, Martinez-Murillo R, Martinez A. SCI REP; 6:33495 (2016). DOI: 10.1038/srep33495
      • Brain local and regional neuroglial alterations in Alzheimer’s disease: cell types, responses and implications. Toledano A, Álvarez MI, Toledano-Díaz A, Merino JJ, Rodríguez JJ.. CURR ALZH RES. 13(4):321-342 (2016). DOI: 10.2174/1567205013666151116141217
      • Blood-based biomarkers of Alzheimer’s disease: diagnostic algorithms and new technologies. Carmona P, Molina M, Toledano A. ICURR ALZH RES.; 13(4):450-464 (2016). DOI: 10.2174/1567205013666151116130301
      • Neuroglia in Alzheimer’s Disease: From Cohort to Contestant in the Disease Progression and its Therapy. Toledano A, Merino JJ, Rodríguez JJ. CURR ALZH RES.; 13(4):318-20 (2016). http://hdl.handle.net/10261/149792
      • New concepts on the functionality of the nervous system: the revolution of the glial cells. ii. Glial responses keys in the pathogenesis and treatment of diseases of snc. Toledano A, Álvarez MI, Toledano-Díaz A, Rodríguez-Arellano JJ. AN REAL ACAD FARM 82, 1:51-67 (2016). ISSN (Online) 1697-4298

        http://hdl.handle.net/10261/150110

      • The sigma 1 Receptor Engages the Redox-Regulated HINT1 Protein to Bring Opioid Analgesia under NMDA Receptor Negative Control. Rodriguez-Munoz, M; Sanchez-Blazquez, P ; Herrero-Labrador, R; Martinez-Murillo, R ; Merlos, M; Vela, JM; Garzon, J. ANTIOXIDANTS & REDOX SIGNALING 22 (10) , pp.799-818 (2015). DOI: 10.1089/ars.2014.5993
      • Vibrational spectroscopic analysis of peripheral blood plasma of patients with Alzheimer’s disease. Carmona P, Molina M, López-Tobar E, Toledano A.
        ANAL BIOANAL CHEM 407 (25):7747-56 (2015). DOI: 10.1007/s00216-015-8940-7
      • Astroglial cell subtypes in the cerebella of normal adults, elderly adults, and patients with Alzheimer’s disease: a histological and immunohistochemical comparison. Alvarez MI, Rivas L, Lacruz C, Toledano A.. GLIA 63(2):287-312. (2015). DOI: 10.1002/glia.22751
      • Ultrastructural changes in the progress of natural Scrapie regardless fixation protocol. Casanova-Carvajal, O; Zeinoun, M; Urbano-Bojorge, AL; Bacha, F; Livi, JS; Agudo, E; Vargas, G; Sarasa R, Junquera C, Toledano A, Badiola JJ, Monzón M. HISTOCHEM CELL BIOL144 (1):77-85 (2015). DOI 10.1007/s00418-015-1314-6
      • New concepts on the functionality of the nervous system: the revolution of the glial cells. I. The neuro-glial relationships. Toledano A, Álvarez MI, Toledano-Díaz A. AN REAL ACAD FARM VOL. 81, 1:11-18 (2015). ISSN (Online) 1697-4298. http://hdl.handle.net/10261/155110
      • About the vibrational spectroscopy in the diagnosis of Alzheimer’s disease. Carmona P, López-Tobar E, Molina M, Toledano A. AN REAL ACAD FARM. 81, 1:19 –24 (2015). http://hdl.handle.net/10261/128196
      • Methamphetamine Causes Degeneration of Dopamine Cell Bodies and Terminals of the Nigrostriatal Pathway Evidenced by Silver Staining. Ares-Santos, S; Granado, N; Espadas, I; Martinez-Murillo, R; Moratalla, R. NEUROPSYCHOPHARMACOLOGY 39 (5), pp.1066-1080 (2014). DOI: 10.1038/npp.2013.307
      • Donepezil plus propargylamine+8-hydroxyquinoline hybrids as new multifunctional metal-chelators, ChE and MAO inhibitors for the potential treatment of Alzheimer’s disease. Wang, L ; Esteban, G ; Ojima, M ; Bautista-Aguilera, OM ; Inokuchi, T ; Moraleda, I ; Iriepa, I ; Samadi, A ; Youdim, MBH ; Romero, A ; Soriano, E ; Herrero, R ; Fernandez, APF ; Ricardo-Martinez-Murillo ; Marco-Contelles, J ; Unzeta M. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY: 80: 543-561(2014). DOI: 10.1016/j.ejmech.2014.04.078
      • Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury. Genis, Laura; Davila, David; Fernandez, Silvia; Pozo-Rodrigalvarez, Andrea; Martinez-Murillo, Ricardo; Torres-Aleman, Ignacio. F1000Research 3, pp.28 (2014). DOI: 10.12688/f1000research.3-28.v2
      • Morphological approach to assess the involvement of astrocytes in prion propagation. Hernández RS, Sarasa R, Toledano A, Badiola JJ, Monzón M.
        CELL TISSUE RES. 2014 OCT; 358(1):57-63. (2014). DOI: 10.1007/s00441-014-1928-3
      • Variability in the effects of nicotine on different regions of the brain: changes in the concentration of superoxide dismutase isoforms. Toledano A, Álvarez MI, Toledano-Díaz A. Cent Nerv Syst Agents Med Chem.; 14(1):10-22. (2014). DOI: 10.2174/1871524914666140507162907
      • Does Alzheimer’s disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II). Toledano A, Álvarez MI, López-Rodríguez AB, Toledano-Díaz A, Fernández-Verdecia CI. NEUROLOGIA 29(1):42-55 (2014). DOI: 10.1016/j.nrl.2011.05.004
      • Hypothermia prevents gliosis and angiogenesis development in an experimental model of ischemic proliferative retinopathy. Rey-Funes M, Dorfman VB, Ibarra ME, Pena E, Contartese DS, Goldstein J, Acosta JM, Larrayoz IM, Martinez-Murillo R, Martinez A, Loidl CF. INVEST OPHTHALMOL VIS SCI 23-4-; 54:2836-2846 (2013). DOI: 10.1167/iovs.12-11198
      • Could neurotransmitters influence neurogenesis and neurorepair after stroke?. Sanchez-Mendoza E, Bellver-Landete V, Merino JJ, Gonzalez MP, Martinez-Murillo R, Oset-Gasque MJ. NEUROPATHOL APPL NEUROBIOL 39:722-735 (2013). DOI: 10.1111/nan.12082
      • Discrimination analysis of blood plasma associated with Alzheimer’s disease using vibrational spectroscopy. Carmona P, Molina M, Calero M, Bermejo-Pareja F, Martínez-Martín P, Toledano A. J ALZHEIMERS DIS.; 34(4):911-920 (2013). DOI: 10.3233/JAD-122041

      Contacto

      Where to find us

      Neurovascular research group. Laboratory A-12

      Instituto Cajal CSIC. Avda. Doctor Arce, 37. 28002. Madrid

      Call us

      Phone:

      +34 915 854 714

      Write us

      Email address:

      r.martinez@cajal.csic.es
      jserrano@cajal.csic.es
      apfernandez@cajal.csic.es

      Others

      rojects

      • BRI2 role in neuronal differentiation and the underlying molecular mechanisms: towards an innovative regenerative therapy for Alzheimer’s Disease
        Funding entity: Portugal FCT – Fundaço para a Ciência e a Tecnologia (Portuguese national funding agency for science, research and technology)
        Reference No.: PTDC/BTM-TEC/3792/2021
        Duration: 2022-2024
        IP: Sandra Maria Tavares da Costa Rebelo and Filipa de Sá Martins
      • Contilisant optimization: design, synthesis and biological evaluation
        Funding entity: Ministry of Science, Innovation and Universities
        Reference No.: PID2019-105813RB-C21
        Duration: 2021-2023
        IP: José Luis Marco Contelles and Ricardo Martínez Murillo
      • Molecules for the treatment of complex diseases associated with age
        Funding entity: Ministry of Economy and Competitiveness
        Reference No.: SAF2015-65586-R
        Duration: 2016-2019
        IP: José Luis Marco Contelles and Ricardo Martínez Murillo
      • Neurocentro-CM Technological Center for the Study and Integrated Treatment of Neurological Disorders
        Financing entity: Community of Madrid
        Reference No.: S2017/BMD-3760
        Duration: 2018-2022
        IP: Ricardo Martínez Murillo (Coordinator: Gustavo Víctor Guinea Tortuero)
      • Development of new nanoparticles and protocols for enhanced hyperthermia
        Funding entity: FIS (CIBER-BBN; INTRAMURAL PROGRAM PROJECT)
        Reference No.: CIBER-BBN; INTRAMURAL PROGRAM PROJECT
        Duration: 2014-2015
        IP: Francisco del Pozo Guerrero (Project coordinator: José Javier Serrano Olmedo)
      • Functional relevance of the novel complex, APP/Fe65/PP1, for Alzheimer’s disease
        Funding entity: State Agency, Higher Council for Scientific Research, Ministry of Science and Innovation
        Reference No.: PRI-AIBPT-2011-1188
        Duration: January 2012 – September 2014 IP: Ricardo Martinez Murillo
        Adrenomedullin Peptide in Attention Deficit Hyperactivity Disorder
        Funding entity: Alicia Koplowitz Foundation
        Duration: October 2010 – October 2012
        IP: Ana Patricia Fernandez Fernandez
      • Mechanisms of protection and repair of the neurovascular unit in Alzheimer’s disease
        Funding entity: Ministry of Science and Innovation
        Reference No.: SAF2010-15173
        Duration: January 2011 – September 2014
        IP: Ricardo Martinez Murillo
      • Study of neuroprotective mechanisms in cerebrovascular pathologies
        Financing entity: Ministry of Education and Science
        Reference No.: SAF2007-60010
        Duration: December 2007- December 2010
        IP: Ricardo Martinez Murillo
        Participation in the Neurovascular Network (RENEVAS)
        Funding entity: Carlos III Health Institute (General Sub-directorate of Networks and Cooperative Research Centers). Ministry of Education and Science
        Reference No.: RD06/0026/1001
        Duration: January 2008 – December 2010
        IP: Ricardo Martinez Murillo

      Doctoral Thesis

      Effect of the Nitric Oxide regulators LA-419 and ONO-1714 in a mouse model of focal cerebral infarction. Andrea Pozo Rodrigálvarez (2014). Autonomous University of Madrid. School of Medicine. Grade: Outstanding Cum Laude

      Teaching

      • Master in Neuroscience from the Autonomous University of Madrid (UAM-Cajal Institute, CSIC)
        Subject: Characterization of Neurotransmitters and Neuroactive
      • Substances in the Central Nervous System Immunocytochemistry and Biochemistry (6 ECTS)
        From 1996 to the present
      • Course “Animal and human cells: applications in regenerative medicine”
        Taught by the Complutense University of Madrid
        From 2013 to the present
      • Direction of Final Degree Projects (TFG) and Final Master’s Projects (TFM)
        Complutense University of Madrid, Autonomous University of Madrid,
        University of Alcalá de Henares and University of Florida, College of Medicine
      • Advanced course on Alzheimer’s disease for health personnel
        A Toledano, MI Álvarez, S Toledano-Díaz
      • Approach to the diagnosis of Alzheimer’s disease
        A Toledano, MI Álvarez, S Toledano-Díaz
      • Approach to the treatment of Alzheimer’s disease
        A Toledano, MI Álvarez, S Toledano-Díaz
      • Mental stimulation of Alzheimer’s patients: Occupational Therapy exercises
        J Fernández González, A Toledano, MI Álvarez, S Toledano-Díaz

      Monographs / Books

      • ASS234: A New and Promising Anti-Alzheimer Agent
        Alejandro Romero, Eva Ramos, Ana P. Fernández, Julia Serrano, Ricardo Martínez-Murillo and José Marco-Contelles
        En: Frontiers in Clinical Drug Research – Alzheimer Disorders, Vol. 7, 12-25 Chapter 2 (2018)
        ISSN (Online): 2214-5168 ISSN (Print): 2451-8743
      • Alzheimer pathology in non-human primates and its pathophysiological implications
        Toledano, A.; Álvarez, M.I.; Carmona, P.; Toledano-Díaz, A.; Fernández-Verdecia, C.I.
        En: Primates. Classification, evolution and behavior. E F Hughes and M Hill (Eds). Nova Sciences Pub. New York, pp 71-110 (2012)
        ISBN: 978-1620814987
      • Animal Models of Brain Tumors
        Martínez A., Martinez-Murillo R. (Eds) (2011)
        Springer Science, USA
        ISBN 978-1-62703-209-4
      • Multiple neuronal and glial mechanisms can be involved in the response to the activation of nicotinic receptors
        Toledano A; Alvarez MI; Toledano-Díaz A.
        En: Horizons in Neuroscience Research. Volume 3 Neural Transmissions: Characteristics, Mechanisms and Malfunctioning. A Costa, E Villalba (Eds) Nova Science Publishers, Inc. Hauppauge, NY pp 1-34 (2011)
        ISBN: 978-1-61728-027-6
      • Lesion-induced vertebrate models of Alzheimer Dementia
        A Toledano; Álvarez MI.
        En: Animal models of Dementia. PP Deyn, D Van Dam (Eds). Humana Press, 295-345 (2010)
        ISBN: 978-1-60761-897-3

      Collaborations

      • Gustavo Guinea Tortuero, Centro de Tecnología Biomédica (CTB). Universidad Politécnica de Madrid
      • José Javier Serrano Olmedo, Departamento Tecnología Fotónica y Bioingeniería. Centro de Tecnología Biomédica (CTB). Universidad Politécnica de Madrid
      • Daniel González Nieto, Centro de Tecnología Biomédica (CTB). Universidad Politécnica de Madrid
      • José Luis Marco Contelles, Laboratorio de Radicales Libres y Química Computacional. Instituto de Química Orgánica General (CSIC)
      • Juan Manuel García Segura, CAI de Resonancia Magnética Nuclear. Universidad Complutense de Madrid
      • María del Pilar Herrero Martín, Centro de Tecnología Biomédica (CTB). Universidad Politécnica de Madrid
      • Juan Antonio Barcia Albacar, Hospital Universitario Clínico San Carlos
      • Fivos Panetsos, Facultad de Óptica y Optometría. Universidad Complutense de Madrid
      • Julio Ángel Mayol Martínez, Hospital Universitario Clínico San Carlos
      • Fernando Maestú Unturbe, Facultad de Psicología. Universidad Complutense de Madrid
      • Félix Armadá Maresca, Instituto de Investigación Sanitaria. Hospital Universitario La Paz (IDIPAZ)
      • Sandra Maria Tavares da Costa Rebelo, Universidade de Aveiro
      • Filipa de Sá Martins, Universidade de Aveiro
      • Manuela García López, Instituto Teófilo Hernández. Madrid.
      • Javier Pérez Castells, Departamento de Química Orgánica. Universidad San Pablo-CEU. Madrid
      • Alfredo Martínez, Centro de Investigación Biomédica de la Rioja (CIBIR)
      • César Fabián Loidl, Facultad de Medicina. Universidad de Buenos Aires
      • Manuel Rey Funes, Facultad de Medicina. Universidad de Buenos Aires
      • Carlos Vicario, Departamento de Neurobiología Celular, Molecular y del Desarrollo. Instituto Cajal (CSIC)
      • Gertrudis Perea, Departamento de Neurobiología Funcional y de Sistemas. Instituto Cajal (CSIC)
      • Alfonso Araque, University of Minnesota
      • Rosario Moratalla, Departamento de Neurobiología Funcional y de Sistemas. Instituto Cajal (CSIC)
      • Ignacio Torres, Departamento de Neurobiología Funcional y de Sistemas. Instituto Cajal (CSIC)
      • Javier Garzón, Departamento de Neurociencia Traslacional. Instituto Cajal (CSIC)
      • Pilar Sánchez, Departamento de Neurociencia Traslacional. Instituto Cajal (CSIC)
      • Ignacio Lizasoain, Departamento de Farmacología y Toxicología. Facultad de Medicina. Universidad Complutense de Madrid
      • María Ángeles Moro, Departamento de Farmacología y Toxicología. Facultad de Medicina. Universidad Complutense de Madrid
      • José Julio Rodríguez Arellano, Grupo de Neuroanatomía Funcional (BioCruces- IKERBASQUE)
      • Marta Monzón, Centro de Encefalopatías Espongiformes y Enfermedades Emergentes. Universidad de Zaragoza
      • Juan José Badiola, Centro de Encefalopatías Espongiformes y Enfermedades Emergentes. Universidad de Zaragoza
      • José Joaquín Merino Martín, Facultad de Farmacia. Universidad Complutense de Madrid
      • Adolfo Toledano Díaz, Departamento de Reproducción Animal (INIA-CSIC)
      • Pedro Carmona, Instituto de Estructura de la Materia (CSIC)

      Science dissemination

      • A Toledano, M I Álvarez, S Toledano-Díaz (2008)
        The complex evolution of Alzheimer’s disease during its hundred years of existence: research, clinical and social health care. Acta Cient Tecnol. 13:31-37 
      • A Toledano, MI Álvarez, A Toledano-Díaz. (2007)
        On the centenary of the Nobel Prize for Cajal: the merit and validity of a transcendental scientific work. Acta Cient Tecnol. 12:24-31 
      • A Toledano. (2007)
        Cajal: a Nobel, a scientific work and a revolution in the history of medicine. ACTA 43:9-15
      • Toledano A. (2006)
        Mysterious and dangerous prion diseases or transmissible spongiform encephalopathies: new and revolutionary concepts in pathology. ACTA 41:23-33
      • Toledano A., Alvarez M.I., Toledano S. (2004)
        The REDAFIAL Project of the Alzheimer Foundation Spain and its website http://alzheimer.rediris.es. En Aspectos Socio- sanitarios del Alzheimer. Selmes J., Zaragozá F., Toledano A., Álvarez M.I., Toledano S. (Coordinadores) R. Acad. Farm./Fundación Casares Gil
      • Toledano A. (2003)
        Alzheimer’s disease. The difficult balance between the specific and the generic, the possible and the impossible. Acta Científica y Tecnológica. 7:33-40

      Contracts with companies

      • Study of the benefit of the administration of the product LA419 and its enantiomer LA 455 in a model of affectation of the neurovascular unit; focal myocardial infarction (stroke) and Alzheimer’s disease (PS1A246E-APPSWE)
        Duration: January 2011 – December 2012
      • Commercialization of specific antibodies for neuroscience and other fields of biomedical research produced by the INSTITUTO CAJAL-CSIC
        Duration: 2014 – present

      Funding

        • Ministry of Science and Innovation. Government of Spain
        • Higher Council for Scientific Research (CSIC)
        • Alice Koplowitz Foundation
        • Lacer Laboratories
        • Network Biomedical Research Center. Bioengineering, Biomaterials and Nanomedicine
        • Carlos III Health Institute
        • FCT – Foundation for Science and Technology
        • Ministry of Education, Universities, Science and Spokesperson. Madrid’s community

        Neuroscience Research Center dependent on the CSIC. Founded in 1920 and initially directed by Santiago Ramón y Cajal. World reference in the study of the brain. Custodian of the Cajal Legacy. 

        Activities

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