Neuron-Glia Biology in Health and Disease

Group Leader

Dora Maria Tuna Oliveira Brites

PhD (1988) in Pharmacy (Biochemistry), Universidade de Lisboa
Coordinator Investigator, Faculdade de Farmácia, Universidade de Lisboa
 

The Research

Our goal is to understand the role of glial cells in neurodevelopmental and in the onset/progression of neuroinflammation-associated and age-related neurodegenerative disorders, such as AD, ALS and MS. We focus on questions as to how dysfunctional neurons, reactive astrocytes and activated microglia perturb communication among each other, and how such deregulated mechanisms determine neuronal loss and disease dissemination, by assessing alarmins in the secretome and inflamma-miRNAs in exosomes and ectosomes. A second line of research addresses the relevance of inflammation in oligodendrogenesis and demyelinating disorders. Thirdly, we are evaluating the process of brain infiltration by cancer cells and assessing therapeutic strategies to overcome the blood-brain barrier. We use patient-derived iPSCs and biological samples, genetically engineered mice and 2D/3D cell culture models. Targets and disease mechanisms are used by the group to identify early biomarkers and to develop neuroprotective tools.
senehow they communicate with neurons

image_Research_NeuronGlia

 

 

Ongoing Projects

Source: Project ELA-2015-002, Santa Casa da Misericórdia de Lisboa
Title: Impact of astrocyte-derived microvesicles for motor neuron degeneration or as vehicles of neuroprotective cargoes in ALS
PI: Dora Brites
Period: 2016- 2020

Source: JPCOFUND/003/2015, JPco-fuND, Joint Programme – Neurodegenerative Disease Research, Fundação para a Ciência e Tecnologia
Title: Generation of Improved Cellular and Animal Models for Identification of Disease Phenotype and New Therapeutic Targets of Alzheimer’s Disease (MADGIC)
PI (Portugal): Dora Brites
Period: 2016-2018

Source: JUST/2014/JDRUG/AG/DRUG, European Commission – EU drugs policy (Justice Programme)
Title: Identification and assessment of new psychoactive substances: a European network
PI (Portugal): Dora Brites
Period: 2016- 2018

Source: PGG/018/2016, GILEAD GÉNESE, Portugal
Title:  Role of ectosomes in the spread of HIV infection into the CNS and in HIV-associated dementia pathogenesis
Co-PI: Dora Brites
Period: 2017-2019

Source: Proc. 441.00 HUNGRIA, Foundation for Science and Technology (FCT, Portugal) and Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal (NKFIH, Hungary)
Title: Brain metastasization of breast cancer: from phenotype to pathways and signaling”.
PI (Portugal): Maria Alexandra Brito
Period: 2017-18

Recent Most Relevant Publications

Cunha C, Santos C, Gomes C, Fernandes A, Correia AM, Sebastião AM, Vaz AR, Brites D. Downregulated glia interplay and increased miRNA-155 as promising markers to track ALS at an early stage. Mol Neurobiol 2017. [Epub ahead of print].

Pinto S, Cunha C, Barbosa M, Vaz AR, Brites D. Exosomes from NSC-34 cells transfected with hSOD1-G93A are enriched in miR-124 and drive alterations in microglia phenotype. Front Neurosci 2017; 11: 273.

Falcão AS, Carvalho LA, Lidónio G, Vaz AR, Lucas SD, Moreira R, Brites D. Dipeptidyl vinyl sulfone as a novel chemical tool to inhibit HMGB1/NLRP3-inflammasome and inflamma-miRs in Aβ-mediated microglial inflammation. ACS Chem Neurosci 2017; 8: 89-99.

Pogačnik L, Pirc K, Palmela I, Skrt M, Kim KS, Brites D, Brito MA, Ulrih NP, Silva RFM. Potential for brain accessibility and analysis of stability of selected flavonoids in relation to neuroprotection in vitro. Brain Res 2016; 1651: 17-26.

Barateiro A, Afonso V, Santos G, Cerqueira JJ, Brites D, van Horssen J, Fernandes A. S100B as a biomarker and therapeutic target in multiple sclerosis. Mol Neurobiol 2016; 53: 3976-91.

Group Members

PhD Students

Master Students

  • Ana Rita Ribeiro
  • Catarina Ezequiel
  • Catarina Sequeira
  • Daniela Vizinha
  • Filipa Moreira
  • Mariana Cunha
  • Pedro Pascoal
  • Raquel Vicente

Trainees

  • Rute Padre-Santo
  • Rita Candeias
  • Mariana Cunha