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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 neurodegeneration.
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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 the Alzheimer’s disease-associated Aβ peptide. The involvement of ER-mitochondria crosstalk in apoptotic cell death occurring in this neurodegenerative disorder as well as in other pathological conditions affecting the brain, such as diabetes mellitus, is another focus of our research. |
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| Research Highlights |
| In cultured cortical and hippocampal neurons, we demonstrated for the first time that Aβ, namely oligomeric Aβ, activates an ER stress-mediated apoptotic pathway that occurs by a mitochondria-dependent mechanism. The role of this deleterious ER-mitochondria crosstalk in AD was further supported by data obtained in mitochondrial DNA-depleted cells and cybrids (that recapitulate mitochondrial deficits of AD patients). In addition, we found that GluN2A and GluN2B subunits of N-methyl-D-aspartate receptors (NMDARs) are differentially implicated in oligomeric Aβ-induced ER stress in hippocampal neuronal cultures. |
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| Ongoing Projects |
| 1) Protein quality control and AD-related vascular alterations (collaboration: SM Cardoso). 2) Interplay in AD between endothelial cell dysfunction and neurogenesis in the subgranular zone of dentate gyrus (SGZ) and survival of mature hippocampal neurons, focusing on ER stress (collaboration: J Malva, F Agasse). 3) Role of ER-mitochondria crosstalk in neurodegeneration associated with diabetes mellitus (collaboration: P Moreira). 4) Manipulated dendritic cells as a potential disease-modifying therapeutic strategy for AD (collaboration: T Cruz). 5) Metabolic peptides-mediated signaling in AD (collaboration: L Otvos, USA). |
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| Group members |
| Elisabete B Ferreiro |
Postdoctoral fellowr
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| Rosa MM Resende |
Postdoctoral fellow
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| Sueli C Marques |
| PhD student (Doctoral Programme in Experimental Biology and Biomedicine, PDBEB) |
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| Ana Catarina Fonseca |
PhD student in Cellular Biology (co-supervisor with Sandra M Cardoso)
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| Isaura V Martins |
PhD student (University of Manchester, UK)
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| Ana I Plácido |
| PhD student in Health Sciences (co-supervisor with Paula Moreira) |
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| Collaborations |
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| National |
| Mitochondrial Dysfunction and Cell Death at CNC (AC Rego); Neuroprotection and Neurogenesis in Brain Repair at CNC (J Malva/F Agasse); Structural and Computational Biology at CNC (R Brito); Faculty of Pharmacy, University of Coimbra (T Cruz), Hospital’s of University of Coimbra (HUC), Neurology Service (I Santana); Centro de Estudos Farmacêuticos (L Sá e Melo/MM Silva) and Instituto de Ciências Nucleares Aplicadas à Saúde (ICNAS) (A Abrunhosa) at Coimbra’s University; Institute of Molecular Medicine (IMM), Lisbon’s University (TF 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); Department of Biology, Temple University, Philadelphia, USA (Laszlo Otvos) |
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| Curriculum Vitae |
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Professional Activity:
‘Investigadora Auxiliar’ (2000-present), Instituto de Bioquímica, Faculdade de Medicina, Universidade de Coimbra, Portugal.
Invited Professor of Neuroscience (2008-present) at Escola Superior de Tecnologia da Saúde de Coimbra (ESTESC), Portugal.
Collaborator Professor of Neurosciences (2009-present) Faculdade de Medicina, Universidade de Coimbra, Portugal.
Principal Investigator – Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Portugal.
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Education:
Ph.D in Cell Biology (2000), Universidade de Coimbra, Portugal. |
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Awards:
L’Oreal for Women in Science (2004) supported by L’Oreal Portugal/UNESCO/ FCT
Third Best Poster Presentation Prize at the “Fifth International Congress on Vascular Dementia”, 8-11 November 2007, Budapest, Hungary (1st author).
First prize of “Best Poster Award” at the “First PF2MUC Symposium”, 17 October 2011, Coimbra, Portugal (co-author).
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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:
Ferreiro E, Pereira C. (in press) Endoplasmic reticulum stress: a new playER in tauopathies. J Pathol. (Invited Commentary).
Marques SC, Oliveira CR Pereira CM Outeiro TF. (2011) Epigenetics in neurodegeneration: A new layer of complexity. Prog Neuropsychopharmacol Biol Psychiatry 35, 348-355 (review).
Ferreira IL, Resende R, Ferreiro E, Rego AC, Pereira CF. (2010) Multiple defects in energy metabolism in Alzheimer’s disease. Curr Drug Targets. 11, 1193-1206 (review).
Costa RO, Ferreiro E, Martins I, Santana I, Cardoso SM, Oliveira CR, Pereira CM. (in press) Amyloid β-induced ER stress is enhanced under mitochondrial dysfunction conditions. Neurobiol Aging
Costa RO, Ferreiro E, Cardoso SM, Oliveira CR, Pereira CM. (2010) Endoplasmic reticulum stress-mediated apoptotic pathway induced by Aβ1-40 peptide requires the presence of functional mitochondria. J Alzheimer Dis 20, 625-636.
Resende R, Ferreiro E, Pereira C, Oliveira CR. (2008) ER stress is involved in Aβ-induced GSK-3β activation and tau phosphorylation. J Neurosci Res. 86, 2091-2099.
Resende R, Moreira PI, Proença T, Deshpande A, Busciglio J, Pereira C, Oliveira CR. (2008) Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Free Radic Biol Med. 44, 2051-2057.
Ferreiro E, Oliveira CR, Pereira CM. (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 SM, Oliveira CR, 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.
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