Neurofarmacologia molecular

The Molecular Neuropharmacology Group was founded by Gemma Navarro in 2016. The research of the group focuses on the role of G protein-coupled receptors (GPCRs) as therapeutic targets in neurodegenerative diseases such as Alzheimer’s, Parkinson’s or Huntington’s diseases, or Multiple Sclerosis. In parallel, the group also studies addiction to substances of abuse, like alcohol, cannabinoids, opioids or cocaine. Dr. Navarro set up her own laboratory, with all the infrastructure and equipment to carry out the purposed research.

The group has been awarded with several projects from different funding organizations, such as the “Ministerio de Ciencia Innovación y Cultura”, the “Alzheimer’Association” from USA, La Marató de TV3, CIBERNED, or AGAUR. The group has also directly collaborated with different companies, stablishing research contract with Phytoplant Research or Celtarys Research, among others.

In 2023 Dr. Irene Reyes, a former PhD student of the group, joined as Serra Húnter Lecturer. In 2023, also Dr. Jaume Lillo joined the group as post-doctoral researcher. Professors and researchers of the team teach in the PhD program of Biotechnology, in the Master Program of Molecular Biotechnology and in the Bachelor degrees of Pharmacy and Food Sciences, Biochemistry and Chemistry.

Every year, the Molecular Neuropharmacology Group hosts students from the Master program to carry out the “Master thesis”. 3 Master students have joined every year in the last 5 years, plus 2-3 students/year who perform their Bachelor Thesis. The research group has contributed to the academic and scientific training of 16 PhD students. 11 of them have already defended their theses, all Cum laude, 5 with International Mention, one of them awarded as the “Best Thesis in Catalan” and another one received the PhD Extraordinary award. Nowadays, 5 PhD theses are in progress. Since 2016, 27 Master students have also been trained in the group, promoting the international competitiveness of the Spanish research community.

The group is part of the neuroscience research network CIBERNED (Centro de Investigación en Red de Enfermedades Neurodegenerativas) from Instituto de Salud Carlos III. The group has been recognized as Grup Consolidat SGR “UAB-UB” (Universitat Autònoma de Barcelona-Universitat de Barcelona) by the government of Catalunya (IP: Gemma Navarro). We also belong to the Neurosciences Institute from the University of Barcelona.

-The role of G protein-coupled receptors (GPCRs) as therapeutic targets in neurodegenerative diseases such as Alzheimer’s, Parkinson’s or Huntington’s diseases, or Multiple Sclerosis.

-How GPCRs can modulate addiction to substances of abuse, like alcohol, cannabinoids, opioids or cocaine.

1. Grup UABUB de recerca en Medicina traslacional (GRUABUB21). 2021 SGR 00304. SGRC - Ajuts de Suport als Grups de Recerca de Catalunya (SGR). Contribution: PI: Gemma Navarro. Period: 2022-2024.  40.000 €

2. Mecanismos de acción de los cannabinoides sobre la propagación de agentes patogénicos en amiloidopatías y sinucleinopatías. Ministerio de Ciencia e Innovación. PID2020-113430RB-I00. Contribution: PI: Gemma Navarro. Period: Sept 2021-August 2024. 121.000 €

3. Mecanismos de neuroprotección en enfermedad de Alzheimer mediados por receptores de adenosina y olfativos en células del Sistema Nervioso Central (OLFAD). PID2021-126600OB-I00. Ministerio De Ciencia, Innovación. Gob. de España. PI: Rafael Franco. Period:2022-2025. 200.000 €

4. Potencial de receptores de adenosina A2A/A3 o heterómeros A2A/A3 microgliales como dianas de neuroproteccion en enfermedad de Alzheimer. RTI2018-094204-B-I00. Ministerio de Ciencia, Innovación y Universidades. PI: Rafael Franco. Period: 2018-2022. 198.834 €

5. Efectos protectores del Cannabidiol en ictus neonatal y de adulto: Estudio preclínico detallado de los mecanismos moleculares de acción en un modelo de rata. SAF2017-84117-R. MCOC - Ministerio de Economia y Competitividad, Gobierno de España. Contribution: PI: Gemma Navarro. Period: 2018-2021.  85.547€

6. Monitoring the onset and evolution of neuronal dysfunctions. Alzheimer Association, USA. Alzheimer Association Research Fellowship to promote Diversity. Contribución: PI: Gemma Navarro. Period: 2017-2020. 181.000€

7.  Complejos heteroméricos del receptor sigma 1 en adicción a cocaína. BFU2015-64405-R. Ministerio de Economia y Competitividad, Gobierno de España. PI: Rafael Franco. Period: 2016-2018. 284.350 €

8. GPR55, CB1 and CB2 receptor heteromers: From cell signalling and pharmacology to their potential as targets for neurodegenerative diseases. MCOC - Ministerio de Economia y Competitividad.  PI: Rafael Franco. Period: 2013-2016. 304.200€

9. FMTV - Fundació La Marató de TV3. Cannabinoid receptor heteromeric complexes as therapeutic targets in Parkinson’s disease. PI: Rafael Franco. Period: 2015-2017. 120.000€

10. Targeting proliferation and tumor-microenvironment interactions using bifunctional compounds against cannabinoid and chemokine receptors. FMTV - Fundació La Marató de TV3. PI: Enric I. Canela. Period: 2014-2016. 100.000€

11. Mecanismos de neurodegeneración y nuevas dianas terapéuticas en enfermedades neurodegenerativas. CCEN - Consorcio CIBER del área de Enfermedades Neurodegenerativas (CIBERNED). PI: Rafael Franco. Period: 2006-actualidad. 1. 000.000 €

1. Navarro G.; Gómez-Autet M.; Morales P.; Rebassa J.B.; Llinas Del Torrent C.; Jagerovic N.; Pardo L.; Franco R.; 2024 Homodimerization of CB₂ cannabinoid receptor triggered by a bivalent ligand enhances cellular signaling. Pharmacological Research. IF: 9.1 Q1

2. Llinas Del Torrent C.; Raïch I.; Gonzalez A.; Lillo J.; Casajuana-Martin N.; Franco R.; Pardo L.; Navarro G.*; 2024 Allosterism in the adenosine A_2A and cannabinoid CB₂ heteromer. British Journal of Pharmacology. IF: 6.4 Q1

3. Gioé-Gallo,C.; Ortigueira, S.; Azuaje,J.; Paleo,R.; Majellaro, M.; Raïch, I.; Brea, J.M.; Loza, M.I.; Salas,C.O.; García-Mera, X.; Navarro, G.;* (CA) Sotelo, E.;*2023 Pharmacological Insights Emerging from the Characterization of a Large Collection of Synthetic Cannabinoid Receptor Agonists Designer Drugs. Biomedicine & Pharmacotherapy. IF: 7.5 Q1

4. Rivas-Santisteban, R; Lillo, A; Lillo, J; Rebassa, J.B.; Contesti, J. S.; Saura, C. A.; Franco, R.; Navarro, G. (CA) 2021 N-Methyl-D-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. IF:8.82 Q1 citations:11

5. Raïch I, Rivas-Santisteban R, Lillo A, (...) (12/13) Navarro G* (CA), Franco R*. 2021 Similarities and differences upon binding of naturally occurring Δ9-tetrahydrocannabinol-derivatives to cannabinoid CB1 and CB2 receptors. Pharmacological research IF:10,334 Q1 citations:15

6. Alkozi, H.A., Navarro, G., Franco, R., Pintor, J. 2020 Melatonin and the control of intraocular pressure. Progress in Retinal and eye research. IF: 14,86 Q1 citations:26

7. Navarro, G. ; Varanic, k.; Lillo, A.; (…) Franco,R. (1/13) 2020 Pharmacological data of cannabidioland cannabigerol-type phytocannabinoids acting on cannabinoid CB1 , CB2 and CB1 /CB2 heteromer receptors. Pharmacological Research. IF: 7,65 Q1 citations: 52

8. Gnad, T.; Navarro, G .; Lahesmaa, M.; (…) Pfeifer, A. (2/31) 2020 Adenosine/A2B receptor signaling ameliorates the effects of ageing and counteracts obesity. Cell Metabolism. IF: 21,57 Q1 citations: 69

9. Rivas-Santisteban, R.; Rodriguez-Perez, A.I.; Muñoz, A.; Reyes-Resina, I.; Labandeira-Garc.a, J.L.; Navarro, G.* (CA); Franco, R.* 2020 Angiotensin AT1 and AT2 receptor heteromer expression in the hemilesioned rat model of Parkinson's disease that increases with levodopa-induced dyskinesia. Journal of Neuroinflammation. IF: 5,8 Q1 citations:15

10. Franco R, Reyes-Resina I, Aguinaga D, (…) Navarro G. (CA) (14/14) 2019 Potentiation of cannabinoid signaling in microglia by adenosine A(2A) receptor antagonists. IF: 6,0 Q1 citations:30

11. Navarro, G ; Cordomí, A; Casado-Anguera, V; (…)Ferre, S.(1/12) 2018 Evidence for functional precoupled complexes of receptor heteromers and adenylyl cyclase. Nature Communications. IF: 12,353 Q1 citations: 85

12. Bonaventura J., Navarro G., Casadó-Anguera V., (…) Casadó* V.(2/14) 2015 Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer. Proceedings of the National Academy of Sciences of the United States of America – PNAS. ISSN: 0027-8424 IF: 9.42 Q1 citations 123

• Cell culture: cell lines (HEK-293T, CHO)

• Preparation of primary cultures of neurons, microglia and astrocytes

• Obtention and activation of brain slices

-Analysis of MAPK and AKT phosphorylation

-Analysis of protein expression

• Cloning and mutation of genes of interest

• Cell signaling assays to study receptor activation by fluorescence assays and western blot

-Intracellular cAMP accumulation

-MAPK and AKT phosphorylation

-Intracellular calcium release

-ß-arrestin recruitment

-DMR

• Study of neurodegeneration

-Detection of cytokine release

-Detection of ROS species

-Analysis of neuronal death

• Confocal microscopy

-Immunocytochemistry and immunohistochemistry

-Colocalization assays

-Proximity Ligation Assays (PLA) to detect protein-protein interaction

-Internalization assays

-Study of neurite patterning by immunocytochemistry

• Protein-protein interaction assays by resonance energy transfer techniques and immunodetection

-Bioluminiscence Resonance Energy Transfer (BRET)

-Fluorescence Resonance Energy Transfer (FRET)

-Sequential resonance energy transfer (SRET)

-Bimolecular Fluorescence complementation (BiFC)

-Bimolecular Fluorescence and luminescence complementation (BiFLC)

• Microfluidic devices to study axonal transport

• Ligand binding assays by Homogeneous Time-Resolved FRET (HTRF)

• Study of glial phenotype

-Microglia activation and polarization (M1/M2)

-Astroglia activation

-Oligodendrocyte precursors

• Quantitative real-time RT-PCR

National

-Dr. Carles A. Saura, Univ. Autònoma de Barcelona

-Prof. Mercè. Pallàs and Dr. Cristian Griñán, Univ. de Barcelona

-Prof. JL. Labandeira, Univ. de Santiago de Compostela

-Prof. Leonardo Pardo, Univ. Autònoma de Barcelona

-Dr. Arnau Cordomí, Univ. Autònoma de Barcelona

-Dr. N. Jagerovic and Dr. Paula Morales from IQM-CSIC, Madrid

-Dr. José A. Martínez Orgado, Univ. Autónoma de Madrid

-Dr. E. Sotelo, Univ. De Santiago de Compostela

-Dr. F. Torres, Univ. Autònoma de Barcelona

Companies

-Celtarys Research, Santiago de Compostela

-Phytoplant Research S. L., Córdoba

International

-Dr. Borroto-Escuela and Prof. K. Fuxe from Karolinska Institutet, Sweden

-Dr. R. Pacheco, Fundación Ciencia & Vida, Santiago de Chile

-Dr. Kreutz, Leibnitz Institute of Neurobiolog, Magdeburg, Germany

-Dr. Alexander Pfeifer and Dr. Thorsten Gnad, University of Bonn, Germany

-Dr. Ana M. Sebastiao and Dr. Sandra H. Vaz, Univ. of Lisbon