Neuron-Glia Biology in Health and Disease
Investigator Coordinator, Biochemistry and Human Biology Faculdade de Farmácia, Universidade de Lisboa
The group conducts research on neuron-glia-vascular interactions in brain development and aged-related/neurodegenerative diseases, within Drug Discovery Programme. We use conventional (two-dimensional, 2D) and improved (3D) technologies, fibroblast-astrocyte transdifferentiation, iPSCs-derived neural cells, and humanized transgenic animals as physiological relevant models to study normal neurodevelopment, brain disorders, and drug response. We focus on neuron-, astrocyte- and microglia-derived secretome (including exosomes and their cargo in inflammatory miRNA) to deepen knowledge on neuroinflammation regulation/dysregulation in perinatal injury, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and multiple sclerosis (MS). Well-known markers of cell activated phenotypes and neuro-immune axis drivers are evaluated. Modulation of neurodegeneration, glia reactivity and deregulated cell-to-cell communication is performed with specific antagomiRs and premiRs, novel medicines and repurposing drugs. Specific aims, based on competitive funding and international collaborations, are to: (1) Obtain mechanistic insights and therapeutic opportunities in AD, ALS and MS; (2) Explore neurotoxic properties of ALS astrocytes/microglia and exosomes toward regeneration and neuroprotection; (3) Advance knowledge in brain infiltration by cancer cells and on blood-brain barrier (BBB) breakdown and repair. Translation of our research findings into clinics and impact on Community is pursued.
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
Source: Grant for Multiple Sclerosis Innovation, Merck/EMD Serono
Title: Targeting multiple sclerosis immune- and psycho-pathophysiology by modulation of neuroinflammation
PI: Adelaide Fernandes
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
Source: 02/SAICT/2017 Fundação para a Ciência e a Tecnologia
Title: Development of an autologous exosome-based therapy by engineering microRNAs in microglia and motor-neurons using mice and human models of amyotrophic lateral sclerosis (ALS)
PI: Dora Brites
Period: 2018- 2021
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 early ALS stage. Mol Neurobiol 2018; 55: 4207-24.
Santos G, Barateiro A, Gomes C, Brites D, Fernandes A. Impaired oligodendrogenesis and myelination by elevated S100B levels during neurodevelopment. Neuropharmacology 2018; 129: 69-83.
Figueira I, Tavares L, Jardim C, Costa I, Terrasso AP, Mes J, Gardner R, Becker JD, McDougall G, Stewart D, Filipe A, Kim KS, Brites D, Brito C, Brito MA, Santos CN. Blood-brain barrier transport and neuroprotective potential of blackberry-digested polyphenols – an in vitro study. Eur J Nutr 2017 [Epub ahead of print – doi: 10.1007/s00394-017-1576-y].
Caldeira C, Cunha C, Vaz AR, Falcão AS, Barateiro A, Seixas E, Fernandes A, Brites D. Key aging-associated alterations in primary microglia response to beta-amyloid stimulation. Front Aging Neurosci 2017; 9: 277.
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.
- Cátia Gomes
- Marta Barbosa
- Gonçalo Garcia
- Marta Calado
- Rui M. M. Brito
- Catarina Sequeira
- Daniela Vizinha
- Filipa Moreira
- Marta Afonso
- Raquel Vicente
- Sofia Ferreira
- Rita Candeias
- Sara Pinto