NEUROBIOLOGY OF INFLAMMATION AND DEGENERATION – NeuroID Group
(@ NEUROSCIENCES AND PHARMACOLOGY)
Neuroinflammation is the innate immune response of the central nervous system to harmful stimuli such as infections, ischemia, stress, and trauma. This response involves the activation of glial cells – primarily microglia and astrocytes – leading to the release of inflammatory mediators and the production of reactive oxygen and nitrogen species. Endogenous intracellular molecules released from activated or necrotic cells, known as damage-associated molecular patterns (DAMPs), play a pivotal role in triggering the immune response within the brain. This sterile inflammatory process is a hallmark of various neurological disorders, including epilepsy, Alzheimer’s disease, Parkinson’s disease, and traumatic brain injury. The resulting cycle of sustained inflammation contributes to progressive neurodegeneration and exacerbates disease pathology.
The Neurobiology of Inflammation and Degeneration group investigates the molecular and cellular mechanisms of neuroinflammation, aiming to identify novel therapeutic targets for brain disorders. Current research focuses on the NLRP3 inflammasome (NLRP3) pathway, with the primary goal of understanding how NLRP3 modulation and associated glial cell phenotypes can mitigate disease-related neurodegeneration and improve pathological outcomes, specifically in epilepsy and Alzheimer’s disease.
The studies use a combination of in vitro models – including established cell lines and primary cultures of neurons, astrocytes, and microglia – as well as ex vivo models, such as acute and organotypic brain slices. These approaches are complemented by a range of genomic and proteomic analyses, electrophysiological recordings, and confocal microscopy to further elucidate underlying mechanisms and therapeutic potential.
RESEARCH TEAM
Valente, Cláudia, PhD
GROUP LEADER
Cláudia Alexandra dos Santos Valente de Castro graduated in Chemical Engineering (Biotechnology area) in 1997 by Instituto Superior Técnico (IST) Universidade de Lisboa (Portugal). In 1996, she was an ERASMUS student – 6 months – at the University of Strathclyde in Glasgow (Scotland). In 2003, she completed her PhD in Biotechnology in IST, having worked at the Department of Bioengineering of IST and University of Maryland in Baltimore County (UMBC-USA). She concluded her first post-doctoral study in Developmental Biology in 2007 and the second one in Neurosciences in 2010, with grants from Fundação para a Ciência e Tecnologia, both at Instituto de Medicina Molecular (Lisboa, Portugal).
Currently, she is a tenure researcher at the Instituto de Farmacologia e Neurociências at Faculdade de Medicina da Universidade de Lisboa where she coordinates the group Neurobiology of Inflammation and Degeneration (NeuroID). She is also an invited professor with participation in both undergraduate (Integrated Master in Medicine, neuropharmacology) and graduate (Neuroscience Master/PhD Program, neuroinflammation-related topics) courses.
ORCID ID: 0000-0001-5405-3130
E-mail: cvalentecastro@medicina.ulisboa.pt
Pereira, Ana Sofia, MSc
Researcher
Ana Sofia Sousa Pereira finished her Bachelor’s Degree in Biomedical Engineering in 2021 by Instituto Superior Técnico (IST), Universidade de Lisboa, where, due to its highly multidisciplinary curriculum, she acquired basic knowledge in different areas, such as biology, medicine, physics, chemistry, mathematics, and computation. She concluded her Master’s in Biomedical Engineering in 2024, also at IST, under the specialization area of Tissue Engineering and Regenerative Medicine. During her thesis project she extensively worked with the ex vivo model of epileptogenesis in rhinal cortex-hippocampus organotypic slices and gained experience in molecular-based assays such as western blot, enzyme-linked immunosorbent assay, and immunohistochemistry coupled with confocal microscopy, as well as in electrophysiological recordings. Furthermore, she acquired knowledge in image analysis, macro scripting, data processing and statistical analysis.
Ana is a researcher at NeuroID who uses the ex vivo model of epileptogenesis to unravel the impact of NLRP3 inflammasome inhibition in epileptic-like events and glia reactivity.
ORCID: 0000-0002-3603-374X
E-mail: aspereira@medicina.ulisboa.pt
Ferreira, Tiago, MD
MSc Student
Tiago Miguel Garcia Ferreira is a Medical Student with passion for clinical and basic research. Tiago graduated in Health Sciences, Universidade de Lisboa, in 2020 and, in 2023, he concluded his Master’s in Neurosciences at Faculdade de Medicina, Universidade de Lisboa with the thesis titled “Pyroptotic Deadly Curse of Neurons In Alzheimer’s Disease: Unravelling the role of the NLRP3 Inflammassome”. With this thesis, he achieved high expertise in molecular-based assays, mainly immunohistochemistry coupled to confocal microscopy, western blot and ELISA. He is a 5th year medical student who has actively participated in many different university projects including AIMS Meeting scientific committee, pedagogical council, medicine’s commission course and monitor of anatomy’s practical classes.
Tiago is now completing his Master’s in Medicine, a mandatory requirement at FMUL, within the NeuroID group, evaluating pyroptosis-driven neuronal cell death in human samples derived from patients with Alzheimer’s disease.
ORCID: 0000-0002-9493-321X
E-mail: tiagomferreira@medicina.ulisboa.pt
Olim, Inês, BSc
MSc Student
Inês Llorente de Olim graduated in Molecular and Genetic Biology from Faculdade de Ciências, Universidade de Lisboa, in 2023.
She was integrated at NeuroID to pursue her Master’s in Neuroscience at Faculdade de Medicina, Universidade de Lisboa. She works with primary cultures of astrocytes and neurons and uses western blot and immunocytochemistry to address the role of A2 astrocytes in Aβ-induced neuronal toxicity.
ORCID: 0009-0005-3182-9860
E-mail: ines.olim@medicina.ulisboa.pt
COLLABORATORS
Cristiane Damas Gil, Universidade Federal de São Paulo, Brasil
Eleonora Aronica, University of Amsterdam’s Faculty of Medicine, Netherlands
Federico Herrera, FCUL, Lisbon, Portugal
Graham Sheridan, University of Nottingham, United Kingdom
Hugo Vicente Miranda, NOVA Medical School, Lisbon, Portugal
Julie Ribot, GIMM, Lisbon, Portugal
Merab Kokaia, Lund University, Sweden
Myriam Catalano, Sapienza University of Rome, Italy
Roselia Maria Spanevello, Universidade Federal de Pelotas, Rio Grande do Sul, Brasil
Tarja Malm, University of Eastern Finland, Kuopio, Finland
RECENT PROJECTS
As Principal Investigator:
2025 – 2028: Targeting NLRP3 inflammasome: paving the way towards epileptogenesis amelioration. FCT Call 2023 for R&D projects. Awaiting re-evaluation.
As Task Leader:
2025 – 2028: A novel target for disease-selective antiseizure drug (Number to be attributed).
2022 – 2025: Does context matter for drug action? Contextual dependency of the long-lasting neurobiological and antidepressant actions of psilocybin (PTDC/MED-FAR/4834/2021)
2018 – 2021: In the search of the synaptic mechanism operated by a novel selective antiepileptic drug (PTDC/MED-FAR/30933/2017)
As collaborator:
2024 – 2026: PANERIS: Pan-European Network for Neuroscience Research Infrastructure and Strengthening of Support capacities (HORIZON-WIDERA-2023-ACCESS-04-01, Project number: 101160180).
2020 – 2024: EpiEpiNet: Epileptogenesis and Epilepsy Network: from genes, synapses and circuitries to pave the way for novel drugs and strategies. Twinning action between the University of Lisbon, University of Lund, Sapienza University of Rome, and University of Amsterdam (H2020-WIDESPREAD-05-2017-Twinning, Grant agreement No. 952455).
2016 – 2019: SynaNet: Neurologic and Psychiatric Disorders: from synapses to networks. Twinning action between the University of Lisbon, University of Eastern Finland, Sapienza University of Rome, and Lancaster University (H2020-EU.4.b.).
SELECTED PUBLICATIONS
Ferreira, L. P. S., Valente, C. A., & Gil, C. D. (2025). Annexin A1 in Alzheimer’s disease: A new therapeutic target focusing on neuroinflammation. Neural Regeneration Research. Advance online publication. https://doi.org/10.4103/NRR.NRR-D-25-00505. Quartil (Q): Q2.
Gonzalez-Ramos, A., Berglind, F., Kudláček, J., Rocha, E. R., Melin, E., Sebastião, A. M., Valente, C. A., Ledri, M., Andersson, M., & Kokaia, M. (2024). Chemogenetics with PSAM4-GlyR decreases excitability and epileptiform activity in epileptic hippocampus. Gene Therapy, 1–15. https://doi.org/10.1038/s41434-024-00493-7. Quartil (Q): Q1.
Magalhães, D. M., Stewart, N., Mampay, M., Rolle, S., Moeendarbary, E., Hall, C., Flint, M., Sebastião, A. M., Valente, C. A., Dymond, M., & Sheridan, G. K. (2024). The sphingosine 1-phosphate analogue, FTY720, modulates the lipidomic signature of the mouse hippocampus. Journal of Neurochemistry, 1–30. https://doi.org/10.1111/jnc.16073. Quartil (Q): Q1.
Magalhães, D. M., Mampay, M., Sebastião, A. M., Sheridan, G. K., & Valente, C. A. (2024). Age-related impact of social isolation in mice: Young vs middle-aged. Neurochemistry International, 174, 105678. https://doi.org/10.1016/j.neuint.2024.105678. Quartil (Q): Q2.
Van Zeller, M., Sebastião, A. M., & Valente, C. A. (2022). Microglia depletion from primary glial cultures enables to accurately address the immune response of astrocytes. Biomolecules 12, 666. https://doi.org/10.3390/biom12050666. Quartil (Q): Q1.
Valente, C. A., Meda, F. J., Carvalho, M., & Sebastião, A. M. (2021). A model of epileptogenesis in rhinal cortex-hippocampus organotypic slice cultures. Journal of Visualized Experiments, (169), e61330. https://doi.org/10.3791/61330. Quartil (Q): Q2.
Van Zeller, M., Dias, D., Sebastião, A. M., & Valente, C. A. (2021). NLRP3 inflammasome: A starring role in amyloid-β- and tau-driven pathological events in Alzheimer’s disease. J. Alzheimer’s Dis. 83, 939–961. https://doi.org/10.3233/JAD-210268. Quartil (Q): Q1.
Ribeiro, M., Brigas, H. C., Temido-Ferreira, M., Pousinha, P. A., Regen, T., Santa, C., Coelho, J. E., Marques-Morgado, I., Valente, C. A., Omenetti, S., Stockinger, B., Waisman, A., Manadas, B., Lopes, L. V., Silva-Santos, B., & Ribot, J. C. (2019). Meningeal γδ T cell–derived IL-17 controls synaptic plasticity and short-term memory. Sci. Immunol. 4(40), eaay5199. https://doi.org/10.1126/sciimmunol.aay5199. Quartil (Q): Q1.
Magalhães, D. M., Pereira, N., Rombo, D. M., Beltrão-Cavacas, C., Sebastião, A. M., & Valente, C. A. (2018). Ex vivo model of epilepsy in organotypic slices – A new tool for drug screening. Journal of Neuroinflammation, 15 (1), 203. https://doi.org/10.1186/s12974-018-1225-2. Quartil (Q): Q1.
Morais, T. P., Coelho, D., Vaz, S. H., Sebastião, A. M., & Valente, C. A. (2018). Glycine receptor activation impairs ATP-induced calcium transients in cortical astrocytes. Frontiers in Molecular Neuroscience, 10, 444. https://doi.org/10.3389/fnmol.2017.00444. Quartil (Q): Q1.
Aroeira, R. I., Sebastião, A. M., & Valente, C. A. (2015). BDNF, via truncated TrkB receptor, modulates GlyT1 and GlyT2 in astrocytes. Glia, 63(12), 2181-97. https://doi.org/10.1002/glia.22884. Quartil (Q): Q1.
Jerónimo-Santos, A., Vaz, S. H., Parreira, S., Rapaz-Lérias, S., Caetano, A. P., Buée-Scherrer, V., Castrén, E., Valente, C. A., Blum, D., Sebastião, A. M., & Diogenes, M. J. (2015). Dysregulation of TrkB receptors and BDNF function by amyloid-β peptide is mediated by calpain. Cerebral Cortex. 25(9), 3107-21. https://doi.org/10.1093/cercor/bhu055. Quartil (Q): Q1.