Pharmacological Strategies for Neuroprotection
Our research is mainly focused on the identification of new molecular therapeutic targets to prevent neuronal-degeneration and cognitive-loss. Specifically, we are interested in the role of C-Jun-N-terminal-kinases (JNKs) and protein-tyrosine-phosphatase-1B (PTP1B) in the control of these processes. Through different preclinical mouse models of epilepsy, obesity/type-2-diabetes mellitus and Alzheimer’s disease, we have identified an important effect of Licochalcone-A (LicA) and Epigallocatechin-3-gallate (EGCG) to prevent neurodegeneration and deficits in synaptic plasticity. In addition to intraperitoneal and intranasal injections of these compounds, we are improving new treatment methods. With this purpose, we have developed PEGylated-poly(lactic-co-glycolic)-acid-nanoparticle (NPs) with ascorbic-acid (AA). Besides, we are studying the effects of senolytics, a class of drugs that selectively eliminate senescent cells and are promising candidates for the prevention and treatment of chronic diseases associated with the aging process. Specifically, we are studying the effects of new nutraceutical cocrystals (developed by a research group who is involved in crystal enginnering discipline) in different experimental models (epilepsy and Alzheimer). In particular, we are improving the capacity of Pterovita, a new solid form (cocrystal) of pterostilbene with enhanced chemical and thermal stability, solubility, dissolution rate, oral bioavailability, mechanical properties, etc. This polyphenol may have preventive and therapeutic properties in a long list of human diseases, including neurological disorders.
Technologies & Methods
- Use of conventional and conditional knockout mice for JNK pathway
- Use of mice treated with high fat diet as a model of diabesity
- Alzheimer disease model
- Intraperitoneal injections of kainic acid, used as a model of temporal lobe epilepsy
- Use of transgenic mice APPsw / PS1E9
- Retrovirus production
- Immunofluorescence techniques and Bromodeoxiuridine treatments
- Real-time quantitative PCR (qPCR)
- Western blot techniques
- Generation of PEGylated poly(lactic-co-glycolic) acid nanoparticles with ascorbic acid (AA)
- Behavioral animal tests
- “In vitro” primary neuronal cultures
- Intraperitoneal injections of Licochalcona A (an estrogenic flavonoid extracted from licorice root) and Epigallocatechin-3-gallate (EGCG)
- Oral injections of pterostilbene in a cocrystal form
- Evaluation of insulin resistance
- Intracerebral injections
- Analyses through epifluorescence and confocal microscope, double labeling, Sholl analyses
- Purified neuron cultures and purified glial cultures
- Generation of cocrystal compounds
- Measures the amplification of DNA in real time, gene expression quantification
Research Team
Ester Verdaguer
Associate Professor
Miren Ettcheto
Lecturer
Andres Jimenez
Lecturer
Marina Carrasaco
Early Stage Researcher
Monica Bullo
Full Professor
Gemma Casadesus
Full Professor
Ruben Dario-Castro
Postdoctoral Researcher
Jaume Folch
Associate Professor
Patricia RManzine
PostdoctoralResearcher
Jordi Olloquequi
Assistant Professor
Ana Navarro
Early Stage Researcher
Leila Driouech
Technician
Laura Guzman
Early Stage Researcher
MireiaMillet
Early Stage Researcher
Selected publications
Cano, A., Ettcheto, M., Bernuz, M., Puerta, R., Esteban de Antonio, E., Sánchez-López, E., Souto, E. B., Camins, A., Martí, M., Pividori, M. I., Boada, M., & Ruiz, A. (2023). Extracellular vesicles, the emerging mirrors of brain physiopathology. International Journal of Biological Sciences, 19(3), 721–743. https://doi.org/10.7150/ijbs.79063
Cano, A., Muñoz-Morales, Á., Sánchez-López, E., Ettcheto, M., Souto, E. B., Camins, A., Boada, M., & Ruíz, A. (2023). Exosomes-Based Nanomedicine for Neurodegenerative Diseases: Current Insights and Future Challenges. Pharmaceutics, 15(1), 298. https://doi.org/10.3390/pharmaceutics15010298
Esteruelas, G., Ortiz, A., Prat, J., Vega, E., Muñoz-Juncosa, M., López, M. L. G., Ettcheto, M., Camins, A., Sánchez-López, E., & Pujol, M. (2023a). Novel customized age-dependent corneal membranes and interactions with biodegradable nanoparticles loaded with dexibuprofen. Colloids and Surfaces B: Biointerfaces, 228, 113394. https://doi.org/10.1016/j.colsurfb.2023.113394
Esteruelas, G., Ortiz, A., Prat, J., Vega, E., Muñoz-Juncosa, M., López, M. L. G., Ettcheto, M., Camins, A., Sánchez-López, E., & Pujol, M. (2023b). Novel customized age-dependent corneal membranes and interactions with biodegradable nanoparticles loaded with dexibuprofen. Colloids and Surfaces B: Biointerfaces, 228, 113394. https://doi.org/10.1016/j.colsurfb.2023.113394
Fonseca, C., Ettcheto, M., Bicker, J., Fernandes, M. J., Falcão, A., Camins, A., & Fortuna, A. (2023). Under the umbrella of depression and Alzheimer’s disease physiopathology: Can cannabinoids be a dual-pleiotropic therapy? Ageing Research Reviews, 90, 101998. https://doi.org/10.1016/j.arr.2023.101998
Galindo-Camacho, R. M., Haro, I., Gómara, M. J., Espina, M., Fonseca, J., Martins-Gomes, C., Camins, A., Silva, A. M., García, M. L., & Souto, E. B. (2023). Cell penetrating peptides-functionalized Licochalcone-A-loaded PLGA nanoparticles for ocular inflammatory diseases: Evaluation of in vitro anti-proliferative effects, stabilization by freeze-drying and characterization of an in-situ forming gel. International Journal of Pharmaceutics, 639, 122982. https://doi.org/10.1016/j.ijpharm.2023.122982
Olloquequi, J., Ettcheto, M., Cano, A., Fortuna, A., Bicker, J., Sánchez-Lopez, E., Paz, C., Ureña, J., Verdaguer, E., Auladell, C., & Camins, A. (2023). Licochalcone A: A Potential Multitarget Drug for Alzheimer’s Disease Treatment. International Journal of Molecular Sciences, 24(18), 14177. https://doi.org/10.3390/ijms241814177
Pardo, M., Gregorio, S., Montalban, E., Pujadas, L., Elias-Tersa, A., Masachs, N., Vílchez-Acosta, A., Parent, A., Auladell, C., Girault, J.-A., Vila, M., Nairn, A. C., Manso, Y., & Soriano, E. (2023). Adult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders. Frontiers in Cellular Neuroscience, 17. https://doi.org/10.3389/fncel.2023.1143319
Pérez, R., Burgos, V., Marín, V., Camins, A., Olloquequi, J., González-Chavarría, I., Ulrich, H., Wyneken, U., Luarte, A., Ortiz, L., & Paz, C. (2023). Caffeic Acid Phenethyl Ester (CAPE): Biosynthesis, Derivatives and Formulations with Neuroprotective Activities. Antioxidants, 12(8), 1500. https://doi.org/10.3390/antiox12081500
Rabieipoor, S., Zare, M., Ettcheto, M., Camins, A., & Javan, M. (2023). Metformin restores cognitive dysfunction and histopathological deficits in an animal model of sporadic Alzheimer’s disease. Heliyon, 9(7), e17873. https://doi.org/10.1016/j.heliyon.2023.e17873