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| Cláudia Fragão Pereira |
| Group Leader |
Associate Researcher
Institute of Biochemistry
Faculty of Medicine
University of Coimbra
Portugal |
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Ph. |
+351 239 820190 |
| Fax |
+ 351 239 822776 |
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| Ongoing and future projects |
The main focus of the research that will be developed by the group in the near future is the clarification of the cellular and molecular mechanisms underlying neuronal and vascular dysfunction during the aging process and in age-related neurodegenerative diseases associated with aberrant peptide accumulation, in particular in Alzheimer’s (AD) and Parkinson’s (PD) diseases. Another major aim of our future work is the search for novel neuroprotective and neurorepair strategies for these disorders. The projects will be carried out in collaboration with (inter)national research groups and are based on the group’s background expertise in mitochondrial and endoplasmic reticulum (ER) dysfunction in cell death and on the use of several models (mitochondrial-DNA depleted and cybrid cell lines, primary neuronal and endothelial cultures, transgenic mice, human brain and peripheral samples).
We will continue our efforts to clarify the role of ER stress in Aβ-induced toxicity. We will explore the role of different subunits of NMDARs in Aβ-induced ER stress using Aβ-treated hippocampal neurons and hippocampal slices from AD triple transgenic mice and also analyze post-translational modifications of NMDAR subunits triggered by soluble Aβ (collaboration with Mitochondrial Dysfunction and Cell Death group and WL Klein, USA). We will also investigate the interplay between Aβ-induced vascular degeneration and neurogenesis/survival in the subgranular zone of dentate gyrus (SGZ), focusing on ER stress and the subsequent production of endothelial-derived factors as mediators of neurogenesis. In the 3xTg-AD mouse model of AD we intend to promote neurogenesis and survival of the newly born neurons to enhance cell replacement (collaboration with Neuroprotection and Neurogenesis in Brain Repair group).
At the moment we are lauching a new project that concerns the role of endothelium dysfunction in AD (collaboration with G Perry, USA). Our goal at this point is to look at the effect of Aβ on brain endothelial cells function and subsequent neuronal outcome, focusing on the involvement of mitochondria and angiogenesis growth factors signaling. The impact of aging, hypoxia and diabetes in brain vascular endothelium will be evaluated as (potential) risk factors for the development of AD.
In collaboration with research groups at the Univ. Coimbra (Structural and Computational Biology group at CNC), novel theoretical and computational approaches will be used to identify and synthesize compounds with potential neuronal and endothelial protective activity that will be tested in in vitro and in vivo models of AD.
We aim to search for epigenetic modulation in AD (collaboration with Tiago Outeiro, IMM, Lisbon), by assessing DNA methylation, histone acetylation and microRNA expression of some of the genes that are differently expressed in AD. This will be performed in the brain of the 3xTg-AD mice and in brains and peripheral samples from AD patients (collaboration with University’s Hospital). The relation between these epigenetic modifications and signaling pathways involved in AD pathogenesis will be evaluated.
A new research project has been initiated that is aimed to elucidate the role of autophagy in AD and PD etiopathogenesis. Using in vitro models of the sporadic forms of these diseases (cybrids that recapitulate mitochondrial deficits of AD or PD patients) we will evaluate how mitochondrial dysfunction correlates with the activation of the autophagic pathway of cell death.
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| Group members |
| Cláudia MF Pereira |
| Ph.D. - Group Leader |
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| Sandra Morais Cardoso |
| Ph.D. |
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| Paula Isabel Moreira |
| Ph.D. |
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| Catarina Oliveira |
| M.D.- Consultant |
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| Elisabete Ferreiro |
| PostDoc Students |
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| Rosa Resende |
| Ph.D. Student |
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| Ana Raquel Esteves |
| Ph.D. Student |
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| Daniela Arduíno |
| Ph.D. Student |
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| Sueli Marques |
| Ph.D. Student |
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| Sónia Correia |
| Ph.D. Student |
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| Cristina Carvalho |
| Ph.D. Student |
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| Susana Cardoso |
| Ph.D. Student |
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| Ana Catarina Fonseca |
| M.Sc. Student |
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| Renato Xavier Santos |
| M.Sc. Student |
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| Collaborations |
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| National |
CNC Groups (Ana Cristina Rego / João Malva / Rui Brito / Otília Vieira)
Neurology Service, Hospital’s of University of Coimbra (Isabel Santana / Cristina Januário)
X-PROT, BioCant - Biotechnology Center (Carlos Faro / Isaura Simões)
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| International |
Russell Swerdlow: Department of Neurology, University of Virginia Health System, Charlottesville, USA
George Perry: College of Sciences, University of Texas at San Antonio, Texas, USA
Mark Smith: Institute of Pathology, Case Western Reserve University, Cleveland, USA
Jorge Busciglio: Department of Neurobiology and Behavior, University of California, Irvine, USA
Salvatore Oddo / Frank LaFerla: Department of Neurobiology and Behavior, University of California, Irvine, USA
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| Relevant Publications |
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| Reviews/Book Chapters |
Agostinho P, Oliveira CR (2007) Neuroinflammation and mitochondrial dysfunction in Alzheimer´s and Prion´s diseases. In: "Interaction between neurons and glia in aging and disease", Malva JO, Rego AC, Cunha RA, Oliveira CR eds. Springer Publishers, New York, USA (in press)
Moreira PI, Cardoso SM, Santos MS, Oliveira CR (2006) The key role of mitochondria in Alzheimer's disease. J. Alzheimers Dis. 9, 101-110.
Pereira C, Agostinho P, Moreira PI, Cardoso SM, Oliveira CR (2005) Alzheimer’s disease-associated neurotoxic mechanisms and neuroprotective strategies. Current Drug Targets CNS Neurol. Disord. 4, 383-403.
Cardoso SM, Moreira PI, Agostinho P, Pereira C, Oliveira CR (2005) Neurodegenerative pathways in Parkinson’s disease: therapeutical strategies. Current Drug Targets CNS Neurol. Disord. 4, 405-419.
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| Regular Papers: |
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.
Esteves ARF, Domingues AF, Ferreira IL, Januário C, Swerdlow RH, Oliveira CR, Cardoso SM (2008) Mitochondrial dysfunction occurs in Parkinson’s disease cybrids containing an nt2 neuron-like nuclear background. Mitochondrion. 8, 219-228.
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.
Matos M, Augusto E, Oliveira CR, Agostinho P. Amyloid-beta peptide decreases glutamate uptake in cultured astrocytes: Involvement of oxidative stress and mitogen-activated protein kinase cascades. Neuroscience 156, 898-910.
Moreira PI, Siedlak SL, Wang X, Santos MS, Oliveira CR, Tabaton M, Nunomura A, Szweda LI, Aliev G, Smith MA, Zhu X, Perry G (2007)
Autophagocytosis of mitochondria is prominent in Alzheimer disease. J. Neuropathol. Exp. Neurol. 66, 525-532.
Lopes JP, Oliveira CR, Agostinho P (2007) Role of cyclin-dependent kinase 5 in the neurodegenerative process triggered by amyloid-Beta and prion peptides: implications for Alzheimer's disease and prion-related encephalopathies. Cell Mol Neurobiol. 27, 943-57.
Moreira PI, Santos MS, Sena C, Seiça R, Oliveira CR (2005) Insulin protects against amyloid beta-peptide toxicity in brain mitochondria of diabetic rats. Neurobiol Dis. 18, 628.
Cardoso SM, Santana I, Swerdlow RH, Oliveira CR (2004) Mitochondrial dysfunction of Alzheimer’s disease cybrids enhances Abeta toxicity. J. Neurochem. 89, 1417. |
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| Curriculum Vitae |
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Professional Activity:
Research Associate, 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)
M.Sc in Cell Biology, Faculty of Sciences and Technology, University of Coimbra, Portugal (1994)
B.Sc in Biochemistry, Faculty of Sciences and Technology, University of Coimbra, Portugal (1991) |
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Awards:
“L’Oréal for women in Science” (2004) supported by L’Oréal Portugal/UNESCO/FCT entitled “Cross-talk between mitochondria and endoplasmic reticulum in Alzheimer’s disease. Studies with cybrids”. |
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Outreach Activities:
Coordenator Programa Ciência Viva nas Férias at CNC, University of Coimbra (2004-present)
Coordenator and participant in the activities promoted by CNC in the Center region of Portugal during International Brain Awarness Week (2004-present) and during Science and Technology Awarness Week (2006-present). |
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