PHARMACOLOGICAL STRATEGIES FOR NEUROPROTECTION

Principal Investigators

Carme Auladell

Associate Professor

Prevention of neuronal death by apoptosis in neurodegenerative processes

Antoni Camins

Full professor

Therapeutic strategies for the treatment of Alzheimer’s disease focused on cognitive improvement.

Research team

 

Ester Verdaguer

Associate Professor

 

Miren Ettcheto

Lecturer

 

Andres Jimenez

Lecturer

 

Jordi Olloquequi

Lecturer

 

Triana Espinosa

Early Stage Researcher

 

Marina Carrasaco

Early Stage Researcher

 

Marta Riba

Early Stage Researcher

 

Monica Bullo

Others

 

Oriol Busquets

Others

 

Gemma Casadesus

Others

 

Ruben Dario-Castro

Others

 

Jaume Folch

Others

 

Patricia R. Manzine

Others

 

Research Interest

 

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, Alzheimer’s disease and Huntington’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 also studying the role of JNK isoforms in adult hippocampal neurogenic activity in the different preclinical murine models. To achieve this goal, we use stereotaxic methods to label newborn cells with GAG-GFP to determine the dendritic arborisation along neuronal maturation process. In addition, using intraperitoneal injections of bromodeoxyuridine, we analyze the activity of the different neurogenic subpopulations

Technologies & Methods

 

  • Use of conventional and conditional knockout mice for JNK pathway
  • Use of mice treated with high fat diet as a model diabesity
  • Alzheimer diseases model
  • 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 studies
  • Intraperitoneal injections of kainic acid, used as a model of temporal lobe epilepsy. Intraperitoneal injections of Licochalcona A ( an estrogenic flavanoid extracted from licorice root), used as neuroprotector
  • Evalaution of insulin resistence
  • Use of transgenic mice APPsw / PS1E9
  • Intracerebral injection
  • Analyses through epifluoresence and confocal microscope. Double labelling. Sholl analyses
  • Measures the amplification of DNA in real time. Gene expression quantification
  • Purified neuron cultures and purified glial cultures

Active Projects

 

    • Enfermedades neurodegenerativas. Ministerio de Sanidad y Consumo. CB06/05/0024. Antoni Camins

 

    • Grup de Recerca en Envelliment i Neurodegeneració. Agència de Gestió d’Ajuts Universitaris i de Recerca. 2017SGR625. Carmen Auladell.

Selected Publications

 

    • Bonilla, L., Esteruelas, G., Ettcheto, M., Espina, M., García, M. L., Camins, A., Souto, E. B., Cano, A., & Sánchez-López, E. (2021). Biodegradable nanoparticles for the treatment of epilepsy: From current advances to future challenges. Epilepsia open, 10.1002/epi4.12567. Advance online publication. https://doi.org/10.1002/epi4.12567

 

    • Busquets, O., Carrasco, M., Espinosa-Jiménez, T., Ettcheto, M., Verdaguer, E., Auladell, C., Bullò, M., Camins, A., Pinent, M., Rodríguez-Gallego, E., & Folch, J. (2021). GSPE pre-treatment protects against long-term cafeteria diet-induced mitochondrial and inflammatory affectations in the hippocampus of rats. Nutritional neuroscience, 1–11. Advance online publication. https://doi. org/10.1080/1028415X.2021.1995118

 

    • Busquets, O., Parcerisas, A., Verdaguer, E., Ettcheto, M., Camins,
      A., Beas-Zarate, C., Castro-Torres, R. D., & Auladell, C. (2021).
      c-Jun N-Terminal Kinases in Alzheimer’s Disease: A Possible
      Target for the Modulation of the Earliest Alterations. Journal
      of Alzheimer’s Disease: JAD, 82(s1), S127–S139. https://doi.org/10.3233/JAD-201053

 

    • Cano, A., Ettcheto, M., Espina, M., Auladell, C., Folch, J., Kühne, B. A., Barenys, M., Sánchez-López, E., Souto, E. B., García, M. L., Turowski, P., & Camins, A. (2021). Epigallocatechin-3-gallate PEGylated poly(lactic-co-glycolic) acid nanoparticles mitigate striatal pathology and motor deficits in 3-nitropropionic acid intoxicated mice. Nanomedicine, 16(1), 19–35. https://doi.org/10.2217/nnm-2020-0239

 

    • Cano, A., Turowski, P., Ettcheto, M., Duskey, J. T., Tosi, G., Sánchez-López, E., García, M. L., Camins, A., Souto, E. B., Ruiz, A., Marquié, M., & Boada, M. (2021). Nanomedicine-based technologies and novel biomarkers for the diagnosis and treatment of Alzheimer’s disease: from current to future challenges. Journal of Nanobiotechnology, 19(1), 122. https://doi.org/10.1186/s12951-021-00864-x

 

    • Castro-Torres, R. D., Olloquequi, J., Etchetto, M., Caruana, P., Steele, L., Leighton, K. M., Ureña, J., Beas-Zarate, C., Camins, A., Verdaguer, E., & Auladell, C. (2021). Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells. International Journal of Molecular Sciences, 22(17), 9545. https://doi.org/10.3390/ijms22179545

 

    • Del Amo, L., Cano, A., Ettcheto, M., Souto, E. B., Espina, M., Camins, A., García, M. L., & Sánchez-López, E. (2021). Surface Functionalization of PLGA Nanoparticles to Increase Transport across the BBB for Alzheimer’s Disease. Applied Sciences, 11(9). https://doi.org/10.3390/app11094305

 

    • Ettcheto, M., Cano, A., Sanchez-López, E., Verdaguer, E., Folch, J., Auladell, C., & Camins, A. (2021). Masitinib for the treatment of Alzheimer’s disease. Neurodegenerative Disease Management, 11(4), 263–276. https://doi.org/10.2217/nmt2021-0019

 

    • Ettcheto, M., Sánchez-Lopez, E., Cano, A., Carrasco, M., Herrera, K., Manzine, P. R., Espinosa-Jimenez, T., Busquets, O., Verdaguer, E., Olloquequi, J., Auladell, C., Folch, J., & Camins, A. (2021). Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice. Cell & Bioscience, 11(1), 141. https://doi.org/10.1186/s13578-021-00646-w

 

    • García-Torra, V., Cano, A., Espina, M., Ettcheto, M., Camins, A., Barroso, E., Vazquez-Carrera, M., García, M. L., SánchezLópez, E., & Souto, E. B. (2021). State of the Art on Toxicological Mechanisms of Metal and Metal Oxide Nanoparticles and Strategies to Reduce Toxicological Risks. Toxics, 9(8), 195. https://doi.org/10.3390/toxics9080195

 

    • Gutierrez, L., Folch, A., Rojas, M., Cantero, J. L., Atienza, M., Folch, J., Camins, A., Ruiz, A., Papandreou, C., & Bulló, M. (2021). Effects of Nutrition on Cognitive Function in Adults with or without Cognitive Impairment: A Systematic Review of Randomized Controlled Clinical Trials. Nutrients, 13(11), 3728. https://doi.org/10.3390/nu13113728

 

    • Rao, K., Britton, G. B., Rocha Arrieta, L. L., Garcia-Cairasco, N., Lazarowski, A., Palacios, A., Camins Espuny, A., & Maccioni, R. B. (2021). Translational Research and Drug Discovery for Neurodegeneration: Challenges for Latin America. Journal of Alzheimer’s Disease: JAD, 82(s1), S1–S4. https://doi.org/10.3233/JAD-210245

 

    • Rayatpour, A., Farhangi, S., Verdaguer, E., Olloquequi, J., Ureña, J., Auladell, C., & Javan, M. (2021). The Cross Talk between Underlying Mechanisms of Multiple Sclerosis and Epilepsy May Provide New Insights for More Efficient Therapies. Pharmaceuticals, 14(10), 1031. https://doi.org/10.3390/ph14101031