MECHANISTIC AND THERAPEUTIC APPROACHES IN NEURODEGENERATIVE DISORDERS

Principal Investigators

VERONICA BRITO

Assistant Professor

Epitranscriptomic regulation in brain disorders

SILVIA GINES

Associate Professor

Neuron and glia crosstalk in Huntington’s disease

CRISTINA MALAGELADA

Associate Professor

mTOR signaling dysregulation in neurodegenerative diseases

EULALIA MARTI

Associate Professor

Non-coding RNAs regulatory networks in neurodegenerative diseases

ESTHER PEREZ NAVARRO

Associate Professor

Kinases and Phosphatases in neuronal function and dysfunction

Research team

 

Georgina Escaramis

Postdoctoral Researcher

 

Ana Gamez

Postdoctoral Researcher

 

Genis Campoy

Early Stage Researcher

 

Carla Castany

Early Stage Researcher

 

Marc Espina

Early Stage Researcher

 

Anna Guisado

Early Stage Researcher

 

Marina Herrero

Early Stage Researcher

 

Laura Lopez-Molina

Early Stage Researcher

 

Maria Solaguren

Early Stage Researcher

 

Julia Solana

Early Stage Researcher

 

Leticia Perez

Early Stage Researcher

 

Anika Pupak

Early Stage Researcher

Research Interest

 

This programme focuses on understanding of the mechanisms of neurodegenerative diseases from different angles to integrate this knowledge in designing effective pharmacological and molecular therapies. Research interests include investigating neurodegenerative diseases from the mouse behaviour (motor, cognitive and psychiatric) to the cellular and molecular level. In addition of finding new therapeutic targets we are also interested in identifying biomarkers of the disease progression. To this end, we collaborate with clinicians to obtain blood, fibroblasts and cerebrospinal fluid from patients.

Technologies & Methods

 

  • Behavioural tests to assess cognitive, motor dysfunction and depression-like phenotype.
  • Western Blot, Immunofluorescence, immunoprecipitation, proteomics/phosphoproteomics, intracerebral viral injections, extracellular vesicles isolation techniques, primary neuronal and glial cultures from mice and rats
  • RT-qPCR, non-radioactive northern blot
  • Transcriptomics, bioinformatic and biostatistical pipelines for RNA seq analysis, in vitro functional screening
  • Analysis of dendritic spine density and morphology (Golgi staining and gene-gun dyolistic labelling)
  • Confocal microscopy
  • SUnSET method to analyze protein synthesis
  • Fluorescence-activated nuclear suspension imaging (FANSI)
  • Fluorescence-activated cellular suspension imaging (FACSI)

Featured Projects

 

    • Análisis de ARNs con repeticiones CAG como factores patogénicos en la enfermedad de Huntington: implicaciones translacionales en enfermedades de poliglutamina. Ministerio de Economía y Competitividad. SAF2017-88452-R. Eulalia Marti

 

    • Astrocytes at the hub of neuronal dysfunction in Huntington´s disease: Dissecting the role of ARMS/kidins 220 on astrocyte secretome. EHDN_Seed Fund project 1130_201217.

 

    • Epidemiología y Salud Pública (CIBERESP). Instituto de Salud Carlos III. Ministerio de Ciencia e Innovación. Eulalia Marti

 

    • Exploring the role of RNA editing on the generation of pathogenic huntingtin fragments. Hereditary Disease Foundation. Veronica Brito

 

    • Gliotransmitters and cannabinoid receptors at the hub of cognitive and synaptic plasticity impairments in Huntington’s disease. Fundació La Marató de TV3. Marato/2-02013-30-31-32.

 

    • Interacción CB-Grp78: ¿un nuevo mecanismo regulador de la actividad neuroprotectora de los cannabinoids? (CIBERNED). Instituto de Salud Carlos III. Ministerio de Ciencia e Innovación. P2018-01. Silvia Gines

 

    • La enfermedad de Huntington como una laminopatía: interacción entre cerebro y la periferia. Ministerio de Ciencia, Innovación y Universidades. PID2019-106447RB-I00. Esther Perez Navarro

 

    • ¿La proteína RTP801/REDD1 media la disfunción sináptica en procesos neurodegenerativos?. Ministerio de Economía y Competitividad. SAF2017-88812-R. Cristina Malagelada

 

    • Phospho-proteome analysis of PBMCs in LRRK2 mutation carriers: expansion & validation of findings of the Barcelona LRRK2 Biorepository. Michael J. Fox Foundation for Parkinson’s research. Cristina Malagelada

 

    • Transmitofagia entre astrocitos y neuronas: una nueva forma de comunicación entre neurona y glía en la enfermedad de Huntington?. Ministerio de Ciencia, Innovación y Universidades. RTI2018-094374-B-I00. Silvia Gines

Featured Publications

 

    • Creus-Muncunill, J., Guisado-Corcoll, A., Venturi, V., Pantano, L., Escaramís, G., García de Herreros, M., Solaguren-Beascoa, M., Gámez-Valero, A., Navarrete, C., Masana, M., Llorens, F., Diaz-Lucena, D., Pérez-Navarro, E., & Martí, E. (2021). Huntington’s disease brain-derived small RNAs recapitulate associated neuropathology in mice. Acta Neuropathologica, 141(4), 565–584. https://doi.org/10.1007/s00401-021-02272-9

 

    • Alcalá-Vida, R., Garcia-Forn, M., Castany-Pladevall, C., Creus-Muncunill, J., Ito, Y., Blanco, E., Golbano, A., Crespí-Vázquez, K., Parry, A., Slater, G., Samarajiwa, S., Peiró, S., Di Croce, L., Narita, M., & Pérez-Navarro, E. (2021). Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington’s disease. EMBO Molecular Medicine, 13(2), e12105. https://doi.org/10.15252/emmm.202012105

 

    • Moreno-Delgado, D., Puigdellívol, M., Moreno, E., Rodríguez-Ruiz, M., Botta, J., Gasperini, P., Chiarlone, A., Howell, L. A., Scarselli, M., Casadó, V., Cortés, A., Ferré, S., Guzmán, M., Lluís, C., Alberch, J., Canela, E. I., Ginés, S., & McCormick, P. J. (2020). Modulation of dopamine D1 receptors via histamine H3 receptors is a novel therapeutic target for Huntington’s disease. eLife, 9, e51093. https://doi.org/10.7554/eLife.51093

 

    • Martín-Flores, N., Pérez-Sisqués, L., Creus-Muncunill, J., Masana, M., Ginés, S., Alberch, J., Pérez-Navarro, E., & Malagelada, C. (2020). Synaptic RTP801 contributes to motor-learning dysfunction in Huntington’s disease. Cell Death & Disease, 11(7), 569. https://doi.org/10.1038/s41419-020-02775-5

 

    • Pallarès-Albanell, J., Zomeño-Abellán, M. T., Escaramís, G., Pantano, L., Soriano, A., Segura, M. F., & Martí, E. (2019). A High-Throughput Screening Identifies MicroRNA Inhibitors That Influence Neuronal Maintenance and/or Response to Oxidative Stress. Molecular Therapy – Nucleic Acids, 17, 374–387. https://doi.org/10.1016/j.omtn.2019.06.007

 

    • Brito, V., Giralt, A., Masana, M., Royes, A., Espina, M., Sieiro, E., Alberch, J., Castañé, A., Girault, J. A., & Ginés, S. (2019). Cyclin-Dependent Kinase 5 Dysfunction Contributes to Depressive-like Behaviors in Huntington’s Disease by Altering the DARPP-32 Phosphorylation Status in the Nucleus Accumbens. Biological Psychiatry, 86(3), 196–207. https://doi.org/10.1016/j.biopsych.2019.03.001

 

    • Suelves, N., Miguez, A., López-Benito, S., Barriga, G. G., Giralt, A., Alvarez-Periel, E., Arévalo, J. C., Alberch, J., Ginés, S., & Brito, V. (2019). Early Downregulation of p75NTR by Genetic and Pharmacological Approaches Delays the Onset of Motor Deficits and Striatal Dysfunction in Huntington’s Disease Mice. Molecular Neurobiology, 56(2), 935–953. https://doi.org/10.1007/s12035-018-1126-5

 

    • Creus-Muncunill, J., Badillos-Rodríguez, R., Garcia-Forn, M., Masana, M., Garcia-Díaz Barriga, G., Guisado-Corcoll, A., Alberch, J., Malagelada, C., Delgado-García, J. M., Gruart, A., & Pérez-Navarro, E. (2019). Increased translation as a novel pathogenic mechanism in Huntington’s disease. Brain, 142(10), 3158–3175. https://doi.org/10.1093/brain/awz230

 

    • Fernández-Santiago, R., Martín-Flores, N., Antonelli, F., Cerquera, C., Moreno, V., Bandres-Ciga, S., Manduchi, E., Tolosa, E., Singleton, A. B., Moore, J. H., International Parkinson’s Disease Genomics Consortium, Martí, M. J., Ezquerra, M., & Malagelada, C. (2019). SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease. Movement Disorders, 34(9), 1333–1344. https://doi.org/10.1002/mds.27770

Knowledge transfer & Innovation

 

    • Methods and pharmaceutical composition for the treatment of neurodegerative disease. UBTT0329-E.

 

    • Method for predicting early onset and severity of levodopa induced dyskinesia (LID) in subjects diagnosed of Parkinson disease (PD). UBTT0304.

 

    • Method for predicting the onset of extrapyramidal symptoms (EPS) induced by an antipsicotic-based treatment. AVCRI196.