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

Featured Projects

 

    • Enfermedades neurodegenerativas (CIBERNED). Instituto de Salud Carlos III. Ministerio de Ciencia e Innovación. CB06/05/0024. Antoni Camins

 

    • Modulación de la vía del receptor de la insulina hipocampal como estrategia terapéutica para el tratamiento de la pérdida cognitiva. Ministerio de Economía y Competitividad. SAF2017-84283-R. Investigador principal: Antoni Camins. CoIP Carme Auladell

Featured Publications

 

    • 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

 

    • Ettcheto, M., Busquets, O., Espinosa-Jiménez, T., Verdaguer, E., Auladell, C., & Camins, A. (2020). A Chronological Review of Potential Disease-Modifying Therapeutic Strategies for Alzheimer’s Disease. Current pharmaceutical design, 26(12), 1286–1299. https://doi.org/10.2174/1381612826666200211121416

 

    • Ettcheto, M., Olloquequi, J., Sánchez-López, E., Busquets, O., Cano, A., Manzine, P. R., Beas-Zarate, C., Castro-Torres, R. D., García, M. L., Bulló, M., Auladell, C., Folch, J., & Camins, A. (2020). Benzodiazepines and Related Drugs as a Risk Factor in Alzheimer’s Disease Dementia. Frontiers in aging neuroscience, 11, 344. https://doi.org/10.3389/fnagi.2019.00344

 

    • Busquets, O., Parcerisas, A., Verdaguer, E., Ettcheto, M., Camins, A., Beas-Zarate, C., Castro-Torres, R. D., & Auladell, C. (2020). 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, 10.3233/JAD-201053. Advance online publication. https://doi.org/10.3233/JAD-201053

 

    • Ettcheto, M., Sánchez-López, E., Gómez-Mínguez, Y., Cabrera, H., Busquets, O., Beas-Zarate, C., García, M. L., Carro, E., Casadesus, G., Auladell, C., Carrera, M. V., Folch, J., & Camins, A. (2020). Correction to: Peripheral and Central Effects of Memantine in a Mixed Preclinical Mice Model of Obesity and Familial Alzheimer’s Disease. Molecular neurobiology, 57(6), 2887–2888. https://doi.org/10.1007/s12035-020-01918-1

 

    • Ettcheto, M., Cano, A., Manzine, P. R., Busquets, O., Verdaguer, E., Castro-Torres, R. D., García, M. L., Beas-Zarate, C., Olloquequi, J., Auladell, C., Folch, J., & Camins, A. (2020). Epigallocatechin-3-Gallate (EGCG) Improves Cognitive Deficits Aggravated by an Obesogenic Diet Through Modulation of Unfolded Protein Response in APPswe/PS1dE9 Mice. Molecular neurobiology, 57(4), 1814–1827. https://doi.org/10.1007/s12035-019-01849-6

 

    • Castro-Torres, R., Busquets, O., Parcerisas, A., Verdaguer, E., Olloquequi, J., Ettcheto, M., Beas-Zarate, C., Folch, J., Camins, A., & Auladell, C. (2020). Involvement of JNK1 in Neuronal Polarization During Brain Development. Cells, 9(8), 1897. https://doi.org/10.3390/cells9081897

 

    • Ettcheto, M., Busquets, O., Cano, A., Sánchez-Lopez, E., Manzine, P. R., Espinosa-Jimenez, T., Verdaguer, E., Sureda, F. X., Olloquequi, J., Castro-Torres, R. D., Auladell, C., Folch, J., Casadesús, G., & Camins, A. (2020). Pharmacological Strategies to Improve Dendritic Spines in Alzheimer’s Disease. Journal of Alzheimer’s disease : JAD, 10.3233/JAD-201106. Advance online publication. https://doi.org/10.3233/JAD-201106

 

    • Cano, A., Ettcheto, M., Espina, M., López-Machado, A., Cajal, Y., Rabanal, F., Sánchez-López, E., Camins, A., García, M. L., & Souto, E. B. (2020). State-of-the-art polymeric nanoparticles as promising therapeutic tools against human bacterial infections. Journal of Nanobiotechnology, 18(1), 156. https://doi.org/10.1186/s12951-020-00714-2

 

    • Ettcheto, M., Cano, A., Busquets, O., Manzine, P. R., Sánchez-López, E., Castro-Torres, R. D., Beas-Zarate, C., Verdaguer, E., García, M. L., Olloquequi, J., Auladell, C., Folch, J., & Camins, A. (2019). A metabolic perspective of late onset Alzheimer’s disease. Pharmacological research, 145, 104255. https://doi.org/10.1016/j.phrs.2019.104255

 

    • Busquets, O., Ettcheto, M., Eritja, À., Espinosa-Jiménez, T., Verdaguer, E., Olloquequi, J., Beas-Zarate, C., Castro-Torres, R. D., Casadesús, G., Auladell, C., Bulló, M., Folch, J., & Camins, A. (2019). c-Jun N-terminal Kinase 1 ablation protects against metabolic-induced hippocampal cognitive impairments. Journal of molecular medicine (Berlin, Germany), 97(12), 1723–1733. https://doi.org/10.1007/s00109-019-01856-z

 

    • Castro-Torres, R. D., Landa, J., Rabaza, M., Busquets, O., Olloquequi, J., Ettcheto, M., Beas-Zarate, C., Folch, J., Camins, A., Auladell, C., & Verdaguer, E. (2019). JNK Isoforms Are Involved in the Control of Adult Hippocampal Neurogenesis in Mice, Both in Physiological Conditions and in an Experimental Model of Temporal Lobe Epilepsy. MOLECULAR NEUROBIOLOGY, 56(8), 5856–5865. https://doi.org/10.1007/s12035-019-1476-7

 

    • Busquets, O., Ettcheto, M., Cano, A., R Manzine, P., Sánchez-Lopez, E., Espinosa-Jiménez, T., Verdaguer, E., Dario Castro-Torres, R., Beas-Zarate, C., X Sureda, F., Olloquequi, J., Auladell, C., Folch, J., & Camins, A. (2019). Role of c-Jun N-Terminal Kinases (JNKs) in Epilepsy and Metabolic Cognitive Impairment. International journal of molecular sciences, 21(1), 255. https://doi.org/10.3390/ijms21010255

 

    • Folch, J., Olloquequi, J., Ettcheto, M., Busquets, O., Sánchez-López, E., Cano, A., Espinosa-Jiménez, T., García, M. L., Beas-Zarate, C., Casadesús, G., Bulló, M., Auladell, C., & Camins, A. (2019). The Involvement of Peripheral and Brain Insulin Resistance in Late Onset Alzheimer’s Dementia. Frontiers in aging neuroscience, 11, 236. https://doi.org/10.3389/fnagi.2019.00236