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| Molecular Mechanisms of Disease |
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CLÁUDIA MARIA FRAGÃO PEREIRA, PhD
Domain of Specialization
The 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: S.M. Cardoso, P. Moreira); 2) Role of inflammasome activation in ageing and AD (collaboration: T. Cruz, H. Girão); 3) Metabolic peptides-mediated signaling in AD (collaboration: L Otvos, USA); 4) Role of ER-mitochondria crosstalk in neurodegeneration associated with diabetes mellitus (collaboration: P. Moreira). 5) ER stress-mediated interplay between endothelial cell dysfunction and neurogenesis in AD (collaboration: E Ferreiro, J Malva); 6) Role of high-fat diet on cognitive and neuropathological alterations in AD (collaboration: K. Lawrence). |
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| Group members |
| Ana Catarina Fonseca |
PhD student in Cell Biology, FCTUC (co-supervision with Sandra M Cardoso)
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| Ana I Plácido |
| PhD student in Health Sciences, FMUC (co-supervision with Paula Moreira) |
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| Isaura V Martins |
| PhD student, University of Manchester, UK (co-supervision with Katherine Lawrence) |
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| Rosa Resende |
Postdoctoral researcher
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| Former members |
| Elisabete Ferreiro |
PhD student (PhD in Cell Biology, FCTUC) and Post-Doc Fellow
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| Sueli Marques |
| PhD student (Doctoral Programme in Experimental Biology and Biomedicine, University of Coimbra) |
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| Rui O Costa |
PhD student (PhD in Cell Biology, FCTUC)
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| Sílvia Gomes |
Master student (Master in Biology, FCTUC)
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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); Structural and Computational Biology at CNC (R Brito); Faculty of Pharmacy (T Cruz) and Faculty of Medicine (H. Girão), University of Coimbra; University Hospitals of Coimbra (HUC), Neurology Service (I Santana); Institute of Nuclear Sciences Applied to Health (ICNAS) (A Abrunhosa), 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); Faculty of Life Sciences, University of Manchester, UK (Catherine Lawrence). |
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| Curriculum Vitae |
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Professional Activity:
Professor of Neurobiology I (2009-present), Faculty of Sciences and Technology, University of Coimbra, Portugal.
Collaborator in Neurosciences (2009-present), Faculty of Medicine, University of Coimbra, Portugal.
Invited Professor of Neuroscience (2008-present), School of Health Technology of Coimbra (ESTESC), Portugal.
Associate Researcher (2000-present), Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Portugal
Investigator, Center for Neurosciences and Cell Biology, Coimbra, Portugal.
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Education:
PhD in Cell Biology (2000), University of 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:
National Scientific Programme “Ciência Viva – ocupação científica dos jovens nas férias”; International Brain Awarness Week; Science and Technology Awarness Week. |
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| Selected Publications |
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Reviews:
Ferreiro E, Pereira C (2012) Endoplasmic reticulum stress: a new playER in tauopathies. J Pathol. 226: 687-692 (invited commentary)
Ferreiro E, Baldeiras I, Ferreira I, Costa RO, Rego AC, Pereira C, Oliveira CR (2012) Mitochondrial- and endoplasmic reticulum-associated oxidative stress in Alzheimer's disease: from pathogenesis to biomarkers. Int J Cell Biol. 2012: 735206.
Marques SC, Oliveira CR, Pereira CM, Outeiro TF (2011) Epigenetics in neurodegeneration: A new layer of complexity. Prog Neuropsychopharmacol Biol Psychiatry 35: 348-355.
Marques SC, Oliveira CR, Outeiro TF, Pereira CM (2010) Alzheimer's disease: The quest to understand complexity. J Alzheimers Dis. 21: 373-383.
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.
Fonseca AC, Resende R, Oliveira CR, Pereira CM (2010) Cholesterol and statins in Alzheimer’s disease: current controversies. Exp Neurol 223: 282-293.
Cardoso SM, Pereira CF, Moreira PI, Arduino DM, Esteves AR, Oliveira CR (2010) Mitochondrial control of autophagic lysosomal pathway in Alzheimer's disease. Exp Neurol. 223: 294-298.
Regular papers:
Costa RO, Ferreiro E, Oliveira CR, Pereira CF (2012) Inhibition of mitochondrial cytochrome c oxidase potentiates Aβ-induced ER stress and cell death in cortical neurons. Mol Cell Neurosci..
Marques SC, Lemos R, Ferreiro E, Martins M, de Mendonça A, Santana I, Outeiro TF, Pereira CM. (2012) Epigenetic regulation of BACE1 in Alzheimer's disease patients and in transgenic mice. Neuroscience. 220: 256-266.
Mota SI, Ferreira IL, Oliveira CR, Pereira C, Rego AC (2012) Amyloid-beta peptide 1-42 causes microtubule deregulation through N-methyl-D-aspartate receptors in mature hippocampal cultures. Curr Alzheimer Res.
Costa RO, Lacor PN, Ferreira IL, Resende R, Auberson YP, Klein WL, Oliveira CR, Rego AC, Pereira CF (2012) Endoplasmic reticulum stress occurs downstream of GluN2B subunit of N-methyl-D-aspartate receptor in mature hippocampal cultures treated with amyloid-β oligomers. Aging Cell 11: 823-833.
Costa RO, Ferreiro E, Martins I, Santana I, Cardoso SM, Oliveira CR, Pereira CM (2012) Amyloid β-induced ER stress is enhanced under mitochondrial dysfunction conditions. Neurobiol Aging 33: 824.e5-824.e16.
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.
Fonseca AC, Proença T, Resende R, Oliveira CR, Pereira C (2009) Neuroprotective effects of statins in an in vitro model of Alzheimer’s disease. J Alzheimers Dis 17: 503-517.
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.
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