Neuroscience and Disease

RARE Biology Lab

Rare disorders

Neurodevelopmental disorders

RNA-binding proteins

Alzheimer’s disease

Autophagy

Epilepsy

Axons

Dendrites

Synapses


Research lines

To characterize the role of heterogeneous nuclear ribonucleoproteins (hnRNPs) in rare neurodevelopmental disorders

To study the role of intra-axonal autophagy in the pathogenesis of Alzheimer’s disease

Overview

Research in Autophagy and RNA binding proteins-related Etiologies - RARE Biology Lab

The laboratory investigates intra-axonal and dendritic signalling pathways in rat hippocampal and cortical neurons under both physiological and pathological conditions. In particular, our research focuses on how intra-axonal autophagy dysfunction contributes to the onset of Alzheimer’s disease, and on elucidating the roles of RNA-binding proteins in rare neurodevelopmental disorders and epilepsy.

Our experimental approaches integrate a broad range of techniques, including primary neuronal cultures, in vivo nucleic acid transfection (in utero electroporation), in vitro and in vivo pharmacology, biochemical assays, immunocytochemistry, and confocal (live) imaging. We also employ molecular tools such as protein molecular replacement strategies to dissect the functional consequences of disease-associated mutations and to restore normal protein activity in cellular and animal models.

Through these complementary strategies, we aim to advance the understanding of neuronal development and the molecular mechanisms underlying neurodegenerative and neurodevelopmental disorders, ultimately contributing to the identification of innovative therapeutic approaches.

Publications

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Information about journal articles, updated at 12-10-2025, from platform CIÊNCIAVITAE.

Brain-derived neurotrophic factor -induced regulation of RNA metabolism in neuronal development and synaptic plasticity

Rui O. Costa; Luís F. Martins; Emanuel Tahiri; Carlos B. Duarte, 2022. WIREs RNA. 2022. https://doi.org/10.1002/wrna.1713 . 10.1002/wrna.1713 . WIREs RNA

Isolation and Culture of Chick Ciliary Ganglion Neurons

Costa, Filipa J.; Dias, Marta S.; Costa, Rui O.; Pedro, Joana R.; Almeida, Ramiro D., 2020. Journal of Visualized Experiments. 162. 2020. http://dx.doi.org/10.3791/61431 . 10.3791/61431 . Journal of Visualized Experiments

Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons

Costa, Rui O.; Martins, Helena; Martins, Luís F.; Cwetsch, Andrzej W.; Mele, Miranda; Pedro, Joana R.; Tomé, Diogo; et al, 2019. Cell Reports. 864 - 876.e6. 4. 28. 2019. http://dx.doi.org/10.1016/j.celrep.2019.06.080 . 10.1016/j.celrep.2019.06.080 . Cell Reports

Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders

Mele, Miranda; Costa, Rui O.; Duarte, Carlos B., 2019. Frontiers in Cellular Neuroscience. 13. 2019. http://dx.doi.org/10.3389/fncel.2019.00077 . 10.3389/fncel.2019.00077 . Frontiers in Cellular Neuroscience

Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF

Martins, L.F.; Costa, R.O.; Pedro, J.R.; Aguiar, P.; Serra, S.C.; Teixeira, F.G.; Sousa, N.; Salgado, A.J.; Almeida, R.D., 2017. Scientific Reports. 1. 7. 2017. http://www.scopus.com/inward/record.url?eid=2-s2.0-85021292472&partnerID=MN8TOARS . 10.1038/s41598-017-03592-1 . Scientific Reports

The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons

Graciano Leal; Diogo Comprido; Pasqualino de Luca; Eduardo Morais; Luís Rodrigues; Miranda Mele; Ana R. Santos; et al, 2017. eneuro. ENEURO.0268 - 17.2017. 6. 4. 2017. https://doi.org/10.1523/ENEURO.0268-17.2017 . 10.1523/ENEURO.0268-17.2017 . eneuro

Preparation of Primary Cultures of Embryonic Rat Hippocampal and Cerebrocortical Neurons

Salazar, Ivan; Mele, Miranda; Caldeira, Margarida; Costa, Rui; Correia, Bárbara; Frisari, Simone; Duarte, Carlos; Costa RO, 2017. BIO-PROTOCOL. 18. 7. 2017. http://dx.doi.org/10.21769/bioprotoc.2551 . 10.21769/bioprotoc.2551 . BIO-PROTOCOL

PROneurotrophins and CONSequences

Costa, R.O.; Perestrelo, T.; Almeida, R.D., 2017. Molecular Neurobiology. 1 - 18. 2017. http://www.scopus.com/inward/record.url?eid=2-s2.0-85018273843&partnerID=MN8TOARS . 10.1007/s12035-017-0505-7 . Molecular Neurobiology

Visualizing K48 ubiquitination during presynaptic formation by ubiquitination-induced fluorescence complementation (UiFC)

Pinto, M.J.; Pedro, J.R.; Costa, R.O.; Almeida, R.D., 2016. Frontiers in Molecular Neuroscience. JUNE. 9. 2016. http://www.scopus.com/inward/record.url?eid=2-s2.0-84978476683&partnerID=MN8TOARS . 10.3389/fnmol.2016.00043 . Frontiers in Molecular Neuroscience

Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease

Costa, R.O.; Mota, S.I.; Ferreira, I.L.; Santana, I.; Caldeira, G.L.; Padovano, C.; Fonseca, A.C.; et al, 2015. Biochimica et Biophysica Acta - Molecular Basis of Disease. 1428 - 1441. 7. 1852. 2015. http://www.scopus.com/inward/record.url?eid=2-s2.0-84928128412&partnerID=MN8TOARS . 10.1016/j.bbadis.2015.03.015 . Biochimica et Biophysica Acta - Molecular Basis of Disease

Inhibition of mitochondrial cytochrome c oxidase potentiates Aß-induced ER stress and cell death in cortical neurons

Costa, R.O.; Ferreiro, E.; Oliveira, C.R.; Pereira, C.M.F., 2013. Molecular and Cellular Neuroscience. 1 - 8. 52. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84870349573&partnerID=MN8TOARS . 10.1016/j.mcn.2012.09.005 . Molecular and Cellular Neuroscience

Leptin and ghrelin prevent hippocampal dysfunction induced by Aß oligomers

Martins, I.; Gomes, S.; Costa, R.O.; Otvos, L.; Oliveira, C.R.; Resende, R.; Pereira, C.M.F., 2013. Neuroscience. 41 - 51. 241. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84876430099&partnerID=MN8TOARS . 10.1016/j.neuroscience.2013.02.062 . Neuroscience

Endoplasmic reticulum stress occurs downstream of GluN2B subunit of N-methyl-d-aspartate receptor in mature hippocampal cultures treated with amyloid-ß oligomers

Costa, R.O.; Lacor, P.N.; Ferreira, I.L.; Resende, R.; Auberson, Y.P.; Klein, W.L.; Oliveira, C.R.; Rego, A.C.; Pereira, C.M.F., 2012. Aging Cell. 823 - 833. 5. 11. 2012. http://www.scopus.com/inward/record.url?eid=2-s2.0-84866452758&partnerID=MN8TOARS . 10.1111/j.1474-9726.2012.00848.x . Aging Cell

Amyloid ß-induced ER stress is enhanced under mitochondrial dysfunction conditions

Costa, R.O.; Ferreiro, E.; Martins, I.; Santana, I.; Cardoso, S.M.; Oliveira, C.R.; Pereira, C.M.F., 2012. Neurobiology of Aging. 4. 33. 2012. http://www.scopus.com/inward/record.url?eid=2-s2.0-84856951448&partnerID=MN8TOARS . 10.1016/j.neurobiolaging.2011.04.011 . Neurobiology of Aging

Mitochondrial- and endoplasmic reticulum-associated oxidative stress in alzheimers disease: From pathogenesis to biomarkers

Ferreiro, E.; Baldeiras, I.; Ferreira, I.L.; Costa, R.O.; Rego, A.C.; Pereira, C.F.; Oliveira, C.R., 2012. International Journal of Cell Biology. 2012. http://www.scopus.com/inward/record.url?eid=2-s2.0-84863688106&partnerID=MN8TOARS . 10.1155/2012/735206 . International Journal of Cell Biology

ER stress-mediated apoptotic pathway induced by aß peptide requires the presence of functional mitochondria

Costa, R.O.; Ferreiro, E.; Cardoso, S.M.; Oliveira, C.R.; Pereira, C.M.F., 2010. Journal of Alzheimer's Disease. 625 - 636. 2. 20. 2010. http://www.scopus.com/inward/record.url?eid=2-s2.0-77954516455&partnerID=MN8TOARS . 10.3233/JAD-2010-091369 . Journal of Alzheimer's Disease

Involvement of mitochondria in endoplasmic reticulum stress-induced apoptotic cell death pathway triggered by the prion peptide PrP 106-126

Ferreiro, E.; Costa, R.; Marques, S.; Cardoso, S.M.; Oliveira, C.R.; Pereira, C.M.F., 2008. Journal of Neurochemistry. 766 - 776. 3. 104. 2008. http://www.scopus.com/inward/record.url?eid=2-s2.0-38049162500&partnerID=MN8TOARS . 10.1111/j.1471-4159.2007.05048.x . Journal of Neurochemistry

An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity

Ferreiro, E.; Resende, R.; Costa, R.; Oliveira, C.R.; Pereira, C.M.F., 2006. Neurobiology of Disease. 669 - 678. 3. 23. 2006. http://www.scopus.com/inward/record.url?eid=2-s2.0-33747195017&partnerID=MN8TOARS . 10.1016/j.nbd.2006.05.011 . Neurobiology of Disease

Awards

2025

Research Grant, FCT – "Understanding RNA-Binding Protein hnRNPH2 Mutations: Implications for Synaptic Function and Neurodevelopmental Disorders."

FCT call IC&DT/2023, project no. 15671 - COMPETE2030-FEDER-00676600

2024

Best Oral Presentation, 36th National Epileptology Meeting (ENE) – "The RNA-binding protein hnRNPH2: A Novel Player in Epileptogenesis."

2022

Scientific Incentive Grant, Portuguese Epilepsy Foundation (LPCE) – "The RNA-binding protein hnRNPH2: A Novel Player in Epileptogenesis.

2013

Exploratory Research Grant, FCT – "Mechanisms Underlying Ribosomal Regulation in Axonal Development.

EXPL/NEU-NMC/0541/2012

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