Research Interest

Ageing is a significant risk factor for dementia and neurodegenerative diseases. Understanding the molecular basis of these brain circumstances is important for attaining their prevention and treatment. This programme focuses on unveiling the mechanisms implicated in neurodegeneration, including epigenetics and drug addiction. In addition, the validation of new pharmacological targets by using small molecules is one of our deals. Also, it includes the study of some polyglucosan structures that appear in these conditions, to find biomarkers related to them, and to study the neuroimmune interactions at central nervous system interfaces also detecting protein-protein interactions.

Technologies & Methods

• Advanced and Confocal Microscopy
• Behavioral assays: Open Field, Elevated Plus Maze, Novel Object Recognition Test, Morris Water Maze, T-Maze for Mice
• Behaviour assays in mice and C. elegans
• C. elegans (in vitro) as a model in neurodegeneration
• Cell signalling
• Chemotaxic Assay, Motility Assay, Toxicity, among others for C. elegans
• Cloning
• Flow citometry
• Histological techniques
• Image analysis
• Immunohistochemical and immunocytochemical staining
• In situ hybridisation
• Isolation and purification of tissue components
• Mice (in vivo) models of aging (SAMP8) and Alzheimer’ disease (5XFAD)
• Resonant energy transfer techniques
• Proteomic and genomic analysis, including NGS techniques (RNA-Seq, miRNA-seq, among others)
• Proximity Ligation assays
• Scanning Electron Microscopy (SEM)
• Transmission Electron Microscopy (TEM)

Active Projects

• • Ajut per a la intensificació de les activitats de transferència per al curs 2021-22. Modalitat A. Universitat de Barcelona. Christian Griñán.

• • Aplicació i avaluació d’un model híbrid de docència en aula inversa per promoure la millora de l’aprenentatge i de les competències específiques i transversals en Farmacologia i Terapèutica. Institut de Ciències de l’Educació – Universitat de Barcelona. REDICE20-2381. Merce Pallas

• • Efectos protectores del cannabidiol en ictus neonatal y de adulto: estudio preclínico detallado de los mecanismos moleculares de acción en un modelo de rata. Ministerio de Ciencia e Innovación. SAF2017-84117-R. Gemma Navarro.

• •  Enfermedades neurodegenrativas. Ministerio de Sanidad y Consumo. CB06/05/0064. Gemma Navarro.

• • Estudio de la presencia de neo-epítopos en estructuras degenerativas cerebrales y de la existencia en el plasma de anticuerpos naturales dirigidos contra dichos neo-epítopos. Ministerio de Economía y Competitividad. BFU2016-78398-P. Carme Pelegri i Jordi Vilaplana

• • Examinando los cuerpos amiláceos del cerebro humano. Ministerio de Ciencia, Innovación y Universidades. PID2020- 115475GB-I00. Carme Pelegri i Jordi Vilaplana.

• • Mecanismos de acción de los cannabinoides sobre la propagación de agentes patogénicos en amiloidopatias y sinucleinopatia. Ministerio de Ciencia e Innovación. PID2020-113430RB-I00. Gemma Navarro.

• • Modulación de la epóxido hidrolasa soluble (sEH)en cerebro y tejidos perifèricos: papel del eje intestino-cerebro en la neurodegeneración. Ministerio de Ciencia, Innovación y Universidades. PID2019-106285RB-C21. Merce Pallas

• • Monitoring the onset and evolution of neuronal dysfunctions. Alzheimer’s Association. ARFD-17-503612. Gemma Navarro

• • Validación de un candidato first in class inhibidor de la epóxido hidrolasa soluble para el tratamiento de la enfermedad de Alzheimer. Tratamiento y evaluación cognitive. Ministerio de Ciencia e Innovación. PDC2021-121096-C21. Merce Pallas.

• • 5 Confidential agreements.

Selected Publications

• • Codony, S., Calvó-Tusell, C., Valverde, E., Osuna, S., Morisseau, C., Loza, M. I., Brea, J., Pérez, C., Rodríguez-Franco, M. I., Pizarro-Delgado, J., Corpas, R., Griñán-Ferré, C., Pallàs, M., Sanfeliu, C., Vázquez-Carrera, M., Hammock, B. D., Feixas, F., & Vázquez, S. (2021). From the Design to the In Vivo Evaluation of Benzohomoadamantane-Derived Soluble Epoxide Hydrolase Inhibitors for the Treatment of Acute Pancreatitis. Journal of Medicinal Chemistry, 64(9), 5429–5446. https://doi.org/10.1021/acs.jmedchem.0c01601

• • Franco, R., Reyes-Resina, I., & Navarro, G. (2021). Dopamine in Health and Disease: Much More Than a Neurotransmitter. Biomedicines, 9(2), 109. https://doi.org/10.3390/biomedicines9020109

• • Griñán-Ferré, C., Bellver-Sanchis, A., Izquierdo, V., Corpas, R., Roig-Soriano, J., Chillón, M., Andres-Lacueva, C., Somogyvári, M., Sőti, C., Sanfeliu, C., & Pallàs, M. (2021). The pleiotropic neuroprotective effects of resveratrol in cognitive decline and Alzheimer’s disease pathology: From antioxidant to epigenetic therapy. Ageing Research Reviews, 67, 101271. https://doi.org/10.1016/j.arr.2021.101271

• • Griñán-Ferré, C., Bellver-Sanchis, A., Olivares-Martín, M., Bañuelos-Hortigüela, O., & Pallàs, M. (2021). Synergistic Neuroprotective Effects of a Natural Product Mixture against AD Hallmarks and Cognitive Decline in Caenorhabditis elegans and an SAMP8 Mice Model. Nutrients, 13(7), 2411. https://doi.org/10.3390/nu13072411

• • Lillo, A., Lillo, J., Raïch, I., Miralpeix, C., Dosrius, F., Franco, R., & Navarro, G. (2021). Ghrelin and Cannabinoid Functional Interactions Mediated by Ghrelin/CB1 Receptor Heteromers That Are Upregulated in the Striatum From Offspring of Mice Under a High-Fat Diet. Frontiers in Cellular Neuroscience, 15, 786597. https://doi.org/10.3389/fncel.2021.786597

• • Mallo-Abreu, A., Reyes-Resina, I., Azuaje, J., Franco, R., GarcíaRey, A., Majellaro, M., Miranda-Pastoriza, D., García-Mera, X., Jespers, W., Gutiérrez-de-Terán, H., Navarro, G., & Sotelo, E. (2021). Potent and Subtype-Selective Dopamine D2 Receptor Biased Partial Agonists Discovered via an Ugi-Based Approach. Journal of Medicinal Chemistry, 64(12), 8710–8726. https://doi. org/10.1021/acs.jmedchem.1c00704

• • Raïch, I., Rivas-Santisteban, R., Lillo, A., Lillo, J., Reyes-Resina, I., Nadal, X., Ferreiro-Vera, C., de Medina, V. S., Majellaro, M., Sotelo, E., Navarro, G., & Franco, R. (2021). Similarities and differences upon binding of naturally occurring 9- tetrahydrocannabinol-derivatives to cannabinoid CB1 and CB2 receptors. Pharmacological Research, 174, 105970. https://doi. org/10.1016/j.phrs.2021.105970

• • Riba, M., Augé, E., Tena, I., Del Valle, J., Molina-Porcel, L., Ximelis, T., Vilaplana, J., & Pelegrí, C. (2021). Corpora Amylacea in the Human Brain Exhibit Neoepitopes of a Carbohydrate Nature. Frontiers in Immunology, 12, 618193. https://doi.org/10.3389/fimmu.2021.618193

• • Riba, M., Del Valle, J., Augé, E., Vilaplana, J., & Pelegrí, C. (2021). From corpora amylacea to wasteosomes: History and perspectives. Ageing Research Reviews, 72, 101484. https://doi.org/10.1016/j.arr.2021.101484

• • Rivas-Santisteban, R., Lillo, J., Muñoz, A., Rodríguez-Pérez, A. I., Labandeira-García, J. L., Navarro, G., & Franco, R. (2021). Novel Interactions Involving the Mas Receptor Show Potential of the Renin-Angiotensin system in the Regulation of Microglia Activation: Altered Expression in Parkinsonism and Dyskinesia. Neurotherapeutics, 18(2), 998–1016. https://doi.org/10.1007/s13311-020-00986-4

• • Rivas-Santisteban, R., Lillo, A., Lillo, J., Rebassa, J. B., Contestí, J. S., Saura, C. A., Franco, R., & Navarro, G. (2021). N-MethylD-aspartate (NMDA) and cannabinoid CB2 receptors form functional complexes in cells of the central nervous system: insights into the therapeutic potential of neuronal and microglial NMDA receptors. Alzheimer’s Research & Therapy, 13(1), 184. https://doi.org/10.1186/s13195-021-00920-6

• • Rodriguez-Arévalo, S., Bagán, A., Griñán-Ferré, C., Vasilopoulou, F., Pallàs, M., Brocos-Mosquera, I., Callado, L. F., Loza, M. I., Martínez, A. L., Brea, J., Pérez, B., Molins, E., De Jonghe, S., Daelemans, D., Radan, M., Djikic, T., Nikolic, K., HernándezHernández, E., García-Fuster, M. J., García-Sevilla, J. A., … Escolano, C. (2021). Benzofuranyl-2-imidazoles as imidazoline I2 receptor ligands for Alzheimer’s disease. European Journal of Medicinal Chemistry, 222, 113540. https://doi.org/10.1016/j.ejmech.2021.113540

• • Vasilopoulou, F., Rodríguez-Arévalo, S., Bagán, A., Escolano, C., Griñán-Ferré, C., & Pallàs, M. (2021). Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer’s disease mouse model: a comparative study with donepezil. British Journal of Pharmacology, 178(15), 3017–3033. https://doi.org/10.1111/bph.15478

• • Sarroca, S., Gatius, A., Rodríguez-Farré, E., Vilchez, D., Pallàs, M., Griñán-Ferré, C., Sanfeliu, C., & Corpas, R. (2021). Resveratrol confers neuroprotection against high-fat diet in a mouse model of Alzheimer’s disease via modulation of proteolytic mechanisms. Journal of Nutritional Biochemistry, 89, 108569. https://doi.org/10.1016/j.jnutbio.2020.108569

Knowledge transfer & Innovation

• • Compounds as soluble epoxide hydrolase inhibitors. UBTT0307d. Sandra Codony, Christian Griñan-Ferre, Merce Pallas, Santiago Vazquez

• • Phenoxycyclohexylurea derivatives for use in reducing accumulation of amyloid plaques and/or hyperphosphorylation of tau protein. UBTT0307a. Sandra Codony, Christian GriñanFerre, Rosana Leiva, Merce Pallas, Santiago Vazquez

• • Synthetic I2 imidazoline receptor ligands for prevention or treatment of human brain disorders. UBTT0327. Maria Carmen Escolano, Merce Pallas, Christian Griñan-Ferre, Sonia Abas, Luis-Felipe Callado, Jesus A. Garcia

• • Secreted splicing variant of klotho for treating bone disorders. UBTT0426-E. Joan Roig, Miguel Chillon, Assumpcio Bosch, Merce Pallas, Christian Griñan-Ferre