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| Molecular Mechanisms of Disease |
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CLÁUDIA MARIA FRAGÃO PEREIRA, PhD
Domain of Specialization
Endoplasmic reticulum (ER) stress response in Alzheimer´s and Prion’s diseases.
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| Research Interests |
| Our major objective is to investigate ER stress as a primary molecular mechanism leading to neuronal and endothelial dysfunction triggered by Aβ or PrP peptides implicated in Alzheimer’s and Prion’s diseases, respectively. The involvement of ER-mitochondria crosstalk in apoptotic cell death occurring in these neurodegenerative disorders is another focus of our research. |
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| Research Highlights |
| Our in vitro studies showed that Aβ and PrP peptides activate the ER stress-mediated apoptotic pathway by a mitochondrial-dependent process. The role of mitochondrial dysfunction in AD was supported by data obtained in cultured neurons from the triple transgenic mice (3 x Tg-AD) and was further explored using cybrid cells (that recapitulate mitochondrial deficits of AD patients), which have a compromised ability to cope with A-induced ER stress. |
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| Ongoing Projects |
| Explore the role of different subunits of N-methyl-D-aspartate receptors (NMDARs) in Aβ-induced ER stress and analyze post-translational modifications of NMDAR triggered by oligomeric Aβ. Investigate the interplay between Aβ-induced endothelial cell dysfunction and neurogenesis in the subgranular zone of dentate gyrus (SGZ), and survival of mature hippocampal neurons, focusing on ER stress. Evaluate the neuroprotective effect of several drugs, including novel estrogen derivatives, statins and anorexigenic/orexigenic peptides (such as leptin and ghrelin) as potential disease-modifying therapeutics for AD. Search for epigenetic modulation of AD-related genes and correlation with signaling pathways involved in AD pathogenesis. |
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| Group members |
| Elisabete B Ferreiro |
Post-Doc researcher
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| Rosa MM Resende |
Post-Doc researcher
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| Rui O Costa |
| PhD student of Cellular Biology |
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| Sueli C Marques |
| PhD student of Cellular Biology (PDBEB) |
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| Ana Catarina Fonseca |
| PhD student of Cellular Biology |
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| Isaura V Martins |
| Master student of Biochemistry |
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| Ana I Plácido |
| Master student of Cellular and Molecular Biology |
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| Sílvia Gomes |
Master student of Biology
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| Collaborations |
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| National |
| Mitochondrial Dysfunction and Cell Death at CNC (Ana Cristina Rego); Neuroprotection and Neurogenesis in Brain Repair at CNC (João Malva/Fabienne Agasse); Free Radicals and Antioxidants at CNC (João Laranjinha); Structural and Computational Biology at CNC (Rui Brito); Hospital’s of University of Coimbra (HUC), Neurology Service (Isabel Santana); Centro de Estudos Farmacêuticos (Luísa Sá e Melo/Maria Manuel Silva) and Instituto de Ciências Nucleares Aplicadas à Saúde (ICNAS) (Antero Abrunhosa) at Coimbra’s University; Institute of Molecular Medicine (IMM), Lisbon’s University (Tiago F Outeiro). |
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| International |
| Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Institute for Neuroscience, Northwestern University, Evanston, IL, USA (WL Klein); School of Biological Sciences, University of California, Irvine, USA (Jorge Busciglio) |
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| Curriculum Vitae |
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Professional Activity:
Associate Researcher, Institute of Biochemistry, Faculty of Medicine, University of Coimbra (2000-present) |
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Education:
Ph.D in Cell Biology, Faculty of Sciences and Technology, University of Coimbra, Portugal (2000) |
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Awards:
L’Oreal for Women in Science (2004) supported by L’Oreal Portugal/UNESCO/ FCT
Third Best Poster Presentation Prize (2008) supported by The Physiological Society
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Outreach Activities:
Programa Ciência Viva nas Férias de Verão; International Brain Awarness Week; Science and Technology Awarness Week. |
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Selected Publications:
Fonseca A.C., Resende R., Oliveira C.R., Pereira C.M.F. (2009) Cholesterol and statins in Alzheimer’s disease: current controversies. Exp Neurol. (Epub ahead of print. PMID: 19782682)
Fonseca A.C., Proença T., Resende R., Oliveira C.R., Pereira C. (2009) Neuroprotective effects of statins in an in vitro model of Alzheimer’s disease. J Alzheimers Dis 17, 503-517.
Resende R., Ferreiro E., Pereira C., Oliveira C.R. (2008) Neurotoxic effect of oligomeric and fibrillar species of Aβ1-42 peptide. Involvement of ER calcium release in oligomers-induced cell death. Neuroscience 155, 725-737.
Resende R., Ferreiro E., Pereira C., Oliveira C.R. (2008) ER stress is involved in Aβ-induced GSK-3β activation and tau phosphorylation. J. Neurosci. Res. 86, 2091-2099.
Resende R., Moreira P.I., Proença T., Deshpande A., Busciglio J., Pereira C., Oliveira C.R. (2008) Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Free Radic. Biol. Med. 44, 2051-2057.
Ferreiro E., Oliveira C.R., Pereira C.M. (2008) The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway. Neurobiol. Dis. 30, 331-342.
Ferreiro E., Costa R., Marques S., Cardoso S.M., Oliveira C.R., Pereira C. (2008) Involvement of mitochondria in endoplasmic reticulum stress-induced apoptotic cell death pathway triggered by the prion peptide PrP106-126. J. Neurochem. 104, 766-776.
Ferreiro E., Eufrásio A., Pereira C., Oliveira C.R., Rego A.C. (2007) Bcl-2 overexpression protects against amyloid-beta and prion toxicity in GT1-7 neural cells. J. Alzheimers Dis. 12, 223-228.
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