Person: Navarro González De Mesa, Elisa
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First Name
Elisa
Last Name
Navarro González De Mesa
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
Identifiers
15 results
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Now showing 1 - 10 of 15
Item Compounds derived from 3-Alkylamino-1H-indole acrylate, and the use thereof in the treatment of neurodegenerative diseases.(2015) León Martínez, Rafael; Buendia Abaitua, Izaskun; Navarro González De Mesa, Elisa; Michalska Dziama, Patrycja; Gameiro Ros, Isabel; López Vivo, Alicia; Egea Máiquez, Francisco Javier; García López, Manuel; García García, Juan Antonio; Fundacioó para la investigación biomédica del Hospital Universitario de La PrincesaThe inventions relates to the methods for producing derivatives of 3-alkylamino-1-H indole acrylate (I) with transcription factor Nrf2-inducing activity, free radical scavenging activity and neuroprotective ability. The invention also relates to the use of derivatives according to the invention for the treatment of diseases, the pathogenesis of which involves oxidative stress, or diseases involving the deregulation of the activity of phase II genes activated by the factor Nrf2 such as Alzheimer´s disease, Parkinson´s disease, Huntington´s disease, multiple sclerosis, ictus or amyotrophic lateral sclerosis.Item Compuestos derivados de acrilato de 3-alquilamino-1H-indolilo y su uso en el tratamiento de las enfermeadades neurodegenerativas(2016) León Martínez, Rafael; Buendia Abaitua, Izaskun; Navarro González De Mesa, Elisa; Michalska Dziama, Patrycja; Gameiro Ros, Isabel; Egea Máiquez, Franisco Javier; García Lopez, Manuela; García García, Juan Antonio; Fundacion para la investigacion biomedica del Hospital Universitario de La PrincesaThe invent relates to the methods for producing derivates of 3-alkylamino-1H-indole acrylate(I) with transcription factor Nrf2-inducing activity, free radical scavenging activity and neuroprotective ability. The invention also relates to the use of derivatives according to the invention of treatment of diseases, the pathogenesis of which involves oxidative stress, or diseases involving the deregulationof the activity of phase II genes activated by the factor Nrf2, such as Alzheimer´s disease, Parkinson´s disease, Huntington´s disease, multiple sclerosis, ictus or amyotrophic lateral sclerosis.Item The Cannabigerol Derivative VCE-003.2 Exerts Therapeutic Effects in 6-Hydroxydopamine-Lesioned Mice: Comparison with The Classic Dopaminergic Replacement Therapy(Brain Sciences, 2023) Rodríguez-Carreiro, Santiago; Muñoz, Eduardo; Fernández-Ruiz, Javier; Navarro González De Mesa, ElisaBackground: A cannabigerol aminoquinone derivative, so-called VCE-003.2, has been found to behave as a neuroprotective agent (administered both i.p. and orally) in different experimental models of Parkinson’s disease (PD) in mice. These effects were exerted through mechanisms that involved the activation of a regulatory site within the peroxisome proliferator-activated receptor-γ (PPAR-γ). (2) Methods: We are now interested in comparing such neuroprotective potential of VCE-003.2, orally administered, with the effect of the classic dopaminergic replacement therapy with L-DOPA/benserazide in similar conditions, using 6-hydroxydopamine-lesioned mice. (3) Results: The oral administration of VCE-003.2 during 14 days at the dose of 20 mg/kg improved, as expected, the neurological status (measured in motor tests) in these mice. This correlated with a preservation of TH-labelled neurons in the substantia nigra. By contrast, the treatment with L-DOPA/benserazide (during 7 days at 2 mg/kg) was significantly less active in these experimental conditions, in concordance with their profile as a mere symptom-alleviating agent. (4) Conclusions: Our results confirmed again the therapeutic profile of VCE-003.2 in experimental PD and revealed a different and more relevant effect, as a disease modifier, compared to the classic symptom-alleviating L-DOPA treatment. This reinforces the interest in VCE-003.2 for a future clinical development in this disease.Item New melatonin–cinnamate hybrids as multi-target drugs for neurodegenerative diseases: Nrf2-induction, antioxidant effect and neuroprotection(Future Medicinal Chemistry, 2015) Buendia, Izaskun; Navarro González De Mesa, Elisa; Michalska Dziama, Patrycja; Gameiro, Isabel; Egea, Javier; Abril, Sheila; López, Alicia; González-Lafuente, Laura; G. López, Manuela; León Martínez, RafaelNeurodegenerative diseases share many pathological pathways, such as abnormal protein aggregation, mitochondrial dysfunction, extensive oxidative stress and neuroinflammation. Cells have an intrinsic mechanism of protection, the Nrf2 transcriptional factor, known as the master regulator of redox homeostasis. Results: Based on the common features of these diseases we have designed a multi-target hybrid structure derived from melatonin and ethyl cinnamate. The obtained derivatives were Nrf2 inducers and potent-free radical scavengers. These new compounds showed a very interesting neuroprotective profile in several in vitro models of oxidative stress, Alzheimer's disease and brain ischemia. Conclusion: We have designed a new hybrid structure with complementary activities. We have identified compound 5h as an interesting Nrf2 inducer, very potent antioxidant and neuroprotectant.Item Cine en compañía para prevenir enfermedades(2023) Valderrama Conde, María José; Linares Gómez, María; Ayllón Santiago, Tania; De Francisco Martínez, Patricia; Bravo Vázquez, Daniel Antonio; López Ejeda, Noemí; Marrodán Serrano, María Dolores; Juan Chocano, María Del Carmen De; García Redondo, Alberto; Hernández Sánchez, María; López Vázquez de la Torre, Mª de la O ; Alonso Monge, Rebeca María Del Mar; Díez Orejas, Rosalía María; Navarro González De Mesa, Elisa; Ancos Pintado, Raquel ; Campo Moreno, Rosa del ; Rodríguez García, Alba ; García Vicente, Roberto ; Álvarez Sánchez-Redondo, Noemí ; Hernando Ospina, Natalia ; Rodríguez Solana, Patricia ; Pulido Vadillo, Mario ; León Rodríguez, Sergio ; Álvaro Llorente, Laura ; Pedrero Tomé, Roberto ; Alaminos Torres, AnaEl proyecto atiende la necesidad social de colectivos desfavorecidos o en riesgo de exclusión (sin hogar, presidiarios, discapacitados o enfermos mentales, mujeres) de ayuda al conocimiento sobre determinadas enfermedades que les afectan con una incidencia más alta que al resto de población (infecciosas, metabólicas, mentales, derivadas de consumo de drogas o alcohol o malnutrición). Adicionalmente, acusan carencias de compañía, entretenimiento o posibilidad de socialización, derivadas de sus circunstancias vitales. Los estudiantes que cursan titulaciones del ámbito de ciencias y ciencias de la salud profundizan en el aprendizaje de estas enfermedades realizando un servicio a estas personas de acompañamiento e información sobre prevención y/o tratamiento de las mismas. Trabajan en equipos multidisciplinares (distintas titulaciones y cursos) y desarrollan competencias profesionales en salud pública, así como transversales, como colaboración y coordinación en equipo, análisis crítico, expresión oral o diseño de materiales. Las actividades de servicio se llevan a cabo mediante visitas a los centros sociales asociados, donde se acompaña a los colectivos con proyección de películas sobre las enfermedades de interés, realización de juegos y coloquio. El proyecto comenzó en el curso 2017-18 (dentro de la convocatoria INNOVA) y ha ampliado el ámbito de conocimiento (bioquímica, biología molecular, epidemiología, microbiología, nutrición), facultades/organismos (Facultades de Biología, Farmacia, Medicina, Químicas, Hospitales 12 de Octubre y Ramón y Cajal), departamentos (Bioquímica y Biología molecular, Genética, Fisiología y Microbiología, Microbiología y Parasitología, Biodiversidad, Ecología y Evolución), asignaturas / titulaciones de los estudiantes, tipo de enfermedades abordadas y grupos y centros sociales atendido (distintas entidades y Ayuntamiento de Madrid).Item Agmatine, by Improving Neuroplasticity Markers and Inducing Nrf2, Prevents Corticosterone-Induced Depressive-Like Behavior in Mice(Molecular Neurobiology, 2015) Freitas, Andiara E.; Navarro González De Mesa, Elisa; García Lopez, ManuelaAgmatine, an endogenous neuromodulator, is a potential candidate to constitute an adjuvant/monotherapy for the management of depression. A recent study by our group demonstrated that agmatine induces Nrf2 and protects against corticosterone effects in a hippocampal neuronal cell line. The present study is an extension of this previous study by assessing the antidepressant-like effect of agmatine in an animal model of depression induced by corticosterone in mice. Swiss mice were treated simultaneously with agmatine or imipramine at a dose of 0.1 mg/kg/day (p.o.) and corticosterone for 21 days and the daily administrations of experimental drugs were given immediately prior to corticosterone (20 mg/kg/day, p.o.) administrations. Wild-type C57BL/6 mice (Nrf2 (+/+)) and Nrf2 KO (Nrf2 (-/-)) were treated during 21 days with agmatine (0.1 mg/kg/day, p.o.) or vehicle. Twenty-four hours after the last treatments, the behavioral tests and biochemical assays were performed. Agmatine treatment for 21 days was able to abolish the corticosterone-induced depressive-like behavior and the alterations in the immunocontent of mature BDNF and synaptotagmin I, and in the serotonin and glutamate levels. Agmatine also abolished the corticosterone-induced changes in the morphology of astrocytes and microglia in CA1 region of hippocampus. In addition, agmatine treatment in control mice increased noradrenaline, serotonin, and dopamine levels, CREB phosphorylation, mature BDNF and synaptotagmin I immunocontents, and reduced pro-BDNF immunocontent in the hippocampus. Agmatine's ability to produce an antidepressant-like effect was abolished in Nrf2 (-/-) mice. The present results reinforce the participation of Nrf2 in the antidepressant-like effect produced by agmatine and expand literature data concerning its mechanisms of action.Item Subthreshold Concentrations of Melatonin and Galantamine Improves Pathological AD-Hallmarks in Hippocampal Organotypic Cultures(Molecular Neurobiology, 2015) Buendía, I.; Parada, E.; Navarro González De Mesa, Elisa; León Martínez, Rafael; Negredo Madrigal, Pilar; Egea Máiquez, Francisco Javier; García López, ManuelaMelatonin is a neurohormone whose levels are significantly reduced or absent in Alzheimer's disease (AD) patients. In these patients, acetylcholinesterase inhibitors (AChEI) are the major drug class used for their treatment; however, they present unwanted cholinergic side effects and have provided limited efficacy in clinic. Because combination therapy is being extensively used to treat different pathological diseases such as cancer or acquired immune deficiency syndrome, we posed this study to evaluate if melatonin in combination with an AChEI, galantamine, could provide beneficial properties in a novel in vitro model of AD. Thus, we subjected organotypic hippocampal cultures (OHCs) to subtoxic concentrations of β-amyloid (0.5 μM βA) plus okadaic acid (1 nM OA), for 4 days. This treatment increased by 95 % cell death, which was mainly apoptotic as shown by positive TUNEL staining. In addition, the combination of βA/OA increased Thioflavin S aggregates, hyperphosphorylation of Tau, oxidative stress (increased DCFDA fluorescence), and neuroinflammation (increased IL-1β and TNFα). Under these experimental conditions, melatonin (1-1000 nM) and galantamine (10-1000 nM), co-incubated with the toxic stimuli, caused a concentration-dependent neuroprotection; maximal neuroprotective effect was achieved at 1 μM of melatonin and galantamine. Most effective was the finding that combination of sub-effective concentrations of melatonin (1 nM) and galantamine (10 nM) provided a synergic anti-apoptotic effect and reduction of most of the AD-related pathological hallmarks observed in the βA/OA model. Therefore, we suggest that supplementation of melatonin in combination with lower doses of AChEIs could be an interesting strategy for AD patients.Item Compounds derived from 3-Alkylamino-1H-indole acrylate, and the use thereof in the treatment of neurodegenerative diseases.(2015) León Martínez, Rafael; Buendia Abaitua, Izaskun; Navarro González De Mesa, Elisa; Michalska Dziama, Patrycja; Gameiro Ros, Isabel Marina; López Vivo, Alicia; Egea Máiquez, Francisco Javier; García López, Manuela; García García, Juan Antonio; Fundación para la investigación biomédica del Hospital Universitario de La PrincesaThe inventions relates to the methods for producing derivatives of 3-alkylamino-1-H indole acrylate (I) with transcription factor Nrf2-inducing activity, free radical scavenging activity and neuroprotective ability. The invention also relates to the use of derivatives according to the invention for the treatment of diseases, the pathogenesis of which involves oxidative stress, or diseases involving the deregulation of the activity of phase II genes activated by the factor Nrf2 such as Alzheimer´s disease, Parkinson´s disease, Huntington´s disease, multiple sclerosis, ictus or amyotrophic lateral sclerosis.Item Heme-Oxygenase I and PCG-1α Regulate Mitochondrial Biogenesis via Microglial Activation of Alpha7 Nicotinic Acetylcholine Receptors Using PNU282987(Antioxidants and Redox Signaling, 2017) Navarro González De Mesa, Elisa; García López, ManuelaAims: A loss in brain acetylcholine and cholinergic markers, subchronic inflammation, and impaired mitochondrial function, which lead to low-energy production and high oxidative stress, are common pathological factors in several neurodegenerative diseases (NDDs). Glial cells are important for brain homeostasis, and microglia controls the central immune response, where α7 acetylcholine nicotinic receptors (nAChR) seem to play a pivotal role; however, little is known about the effects of this receptor in metabolism. Therefore, the aim of this study was to evaluate if glial mitochondrial energetics could be regulated through α7 nAChR. Results: Primary glial cultures treated with the α7 nicotinic agonist PNU282987 increased their mitochondrial mass and their mitochondrial oxygen consumption without increasing oxidative stress; these changes were abolished when nuclear erythroid 2-related factor 2 (Nrf2) was absent, heme oxygenase-1 (HO-1) was inhibited, or peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) was silenced. More specifically, microglia of animals treated intraperitoneally with the α7 nAChR agonist PNU282987 (10 mg/kg) showed a significant increase in mitochondrial mass. Interestingly, LysMcre-Hmox1Δ/Δ and PGC-1α-/- animals showed lower microglial mitochondrial levels and treatment with PNU282987 did not produce effects on mitochondrial levels. Innovation: Increases in microglial mitochondrial mass and metabolism can be achieved via α7 nAChR by a mechanism that implicates Nrf2, HO-1, and PGC-1α. This signaling pathway could open a new strategy for the treatment of NDDs, such as Alzheimer's, characterized by a reduction of cholinergic markers. Conclusion: α7 nAChR signaling increases glial mitochondrial mass, both in vitro and in vivo, via HO-1 and PCG-1α. These effects could be of potential benefit in the context of NDDs. Antioxid. Redox Signal. 27, 93-105.- Project number: 257
Item La experiencia de la educación en la pandemia, una herramienta para el futuro(2023) Hernández Fisac, Inés; Navarro González De Mesa, Elisa; Sagredo Ezquioga, Onintza; Lago Femia, Eva De; Gómez Cañas, María; Rodríguez Cueto, Carmen Aurora; Gómez Ruiz, María Sagrario; Satta, Valentina; Ramírez Alcázar. María Ángeles; Sanz Zamora. Javier; Hernández Fisac, InésLos últimos tres cursos académicos han quedado marcados, indudablemente, por la pandemia mundial que ha alterado el orden conocido a todos los niveles de nuestra vida, pero también ha cambiado la metodología docente, lo que ha supuesto un reto tanto para los docentes como para los alumnos se han enfrentado a ella. De esta forma, se han establecido puntos de partida para una nueva metodología de trabajo en la que los docentes nos enfrentamos a un alumnado cada vez más virtualizado. Nuestros alumnos han asumido las nuevas tecnologías y las redes sociales como parte de su rutina. De igual modo, su forma de aprender también ha cambiado. Esta virtualización del alumnado se ha producido en un momento que coexiste con un progresivo envejecimiento de la plantilla del profesorado. La plantilla PDI de la UCM, en el año 2021, tenía una edad media de 55,67 años, de los cuales, solo el 46% era personal permanente (según datos del Consejo de Gobierno de marzo de 2021). Esto significa que es una plantilla que irremediablemente tendrá que ser reemplazada, a corto plazo, por un gran número de nuevos docentes, sin el bagaje docente que dan los años de experiencia, pero con ideas frescas y nuevas que poner en marcha. Cómo se afronte esta nueva labor, será determinante para el futuro de nuestra Universidad. Nosotros nos proponemos realizar una reflexión y aprender de nuestra propia experiencia. A través del desarrollo de este proyecto queremos analizar cómo han afectado a los resultados académicos, los dos años de docencia virtual o semipresencial que hemos vivido. Pretendemos identificar las fortalezas de las medidas implementadas, pero también las carencias de un sistema que llegó de manera improvisada y, muchas veces, sin medios suficientes. Tanto el curso 2020-2021, como el curso 2021-2022 pusieron a prueba nuestra institución ya que nos enfrentamos al reto de asumir una docencia absoluta o parcialmente virtualizada. Proponemos un proyecto de innovación docente interfacultativo en el que pretendemos evaluar el efecto que ha tenido la situación pandémica global derivada de la COVID-19 sobre la docencia universitaria, enmarcada dentro de los departamentos de Bioquímica y Biología Molecular de la Facultad de Medicina y Psicobiología y Metodología en CIencias del Comportamiento, de la Facultad de Psicología. Esto nos permitirá buscar diferencias entre las medidas implementadas en diferentes centros y entre varios grados impartidos en el área de las Ciencias de la Salud, pero con un diferente componente práctico, como serían los grados de Medicina, Bioquímica, Fisiología, Podología o Psicología.