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| Molecular Mechanisms of Disease |
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PAULA I. MOREIRA, PhD
Domain of Specialization
Mitochondrial dysfunction, oxidative stress and insulin signaling impairment in brain aging, Alzheimer’s disease and diabetes.
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| Research Interests |
| We are interested in elucidating the role of mitochondria and insulin signaling pathways in neuronal and endothelial (dys)function that occur in brain aging, Alzheimer’s disease (AD) and diabetes-associated neurodegeneration. The clarification of the influence of gender on the molecular mechanisms underlying aging-related changes in the diabetic brain is another goal of our group. We also aim to clarify the potential protective role of insulin, exedin-4, mitochondrial uncoupling protein 2 (UCP2) and mitochondrial/hypoxic preconditioning in the above-mentioned pathological conditions. |
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| Research Highlights |
| We provided evidence that brain mitochondria are a functional bridge between type 2 diabetes and AD, two age-related pathologies. It was also observed that type 1 diabetes and insulin-induced hypoglycemia impact differently mitochondria from brain areas associated with learning and memory. Moreover, we found that mitochondrial preconditioning protects against glucotoxicity; this protective effect being mediated by mitochondrial reactive oxygen species and hypoxia inducible factor 1alpha (HIF-1a). |
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| Ongoing Projects |
| 1) The pathological interaction between diabetes and Alzheimer’s disease: exploring the role of neuronal and brain endothelial mitochondria and uncoupling proteins; 2) Mitochondrial preconditioning: potential protective effect in Alzheimer’s disease; 3) Influence of gender on the molecular mechanisms underlying aging-related changes in diabetic brain: The impact of insulin therapy; 4) The impact of exendin-4 therapy in the molecular mechanisms underlying type 2 diabetes-related long-term brain dysfunction (PI – Ana I. Duarte); 5) Crosstalk between endoplasmic reticulum and mitochondria in diabetes-related neurodegeneration (in collaboration with Cláudia Pereira); 6) UCP2 a new molecular target of SIRT3: Relevance in Alzheimer’s disease (in collaboration with Sandra M Cardoso). |
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| Group members |
| Ana I. Duarte |
Postdoctoral fellow
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| Ana Plácido |
| PhD student in Health Sciences (Co-supervisor with Cláudia Pereira) |
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| Cristina Carvalho |
PhD student in Cellular Biology
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| Emanuel Candeias |
MSc, BI fellow
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| Renato X. Santos |
PhD student in Cellular Biology
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| Sónia C. Correia |
PhD student in Cellular Biology
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| Susana Cardoso |
PhD student in Cellular Biology
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| Collaborations |
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| National |
| Mitochondrial Toxicology and Disease Group - CNBC, Universidade de Coimbra (Paulo Oliveira, Sancha Santos); Medical School/IBILI, Universidade de Coimbra (Cristina Sena, Raquel Seiça, Rosa Fernandes); Serviço de Neurologia dos Hospitais da Universidade de Coimbra (Inês Baldeiras); Escola de Ciências da Saúde, Universidade da Beira Interior (Marco Alves, Carlos Pedro Oliveira); Escola de Ciências da Vida e do Ambiente, Universidade de Trás-os-Montes e Alto Douro (Romeu Videira, Francisco Peixoto); Faculdade de Farmácia, Universidade do Porto (Jorge Oliveira – collaboration with Ana I. Duarte) |
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| International |
| Institute of Pathology, Case Western Reserve University, USA (Gemma Casadesus, Joseph LaManna, Xiongwei Zhu); College of Sciences, University of Texas at San Antonio, USA (George Perry); Wallenberg Neuroscience Center, Neuronal Survival Unit, Lund Medical School, Lund, Sweden (Maria Björkqvist – collaboration with Ana I. Duarte) |
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| Curriculum Vitae |
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Professional Activity:
Assistant Professor - Instituto de Fisiologia, Faculdade de Medicina, Universidade de Coimbra, Portugal
Principal Investigator – Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Portugal |
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Education:
PhD in Biomedical Sciences, Universidade de Coimbra, Portugal |
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Awards:
L’Oreal for Women in Science (2008) supported by L’Oreal Portugal/UNESCO/ FCT
Stimulus to Research (2003) supported by Fundação Calouste Gulbenkian
Best Poster Presentation Prize (2003) supported by The Physiological Society
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Selected Publications:
Zhu X, Castellani RJ, Moreira PI, Aliev G, Shenk JC, Siedlak SL, Harris PL, Fujioka H, Sayre LM, Szweda PA, Szweda LI, Smith MA, Perry G. Hydroxynonenal-generated crosslinking fluorophore accumulation in Alzheimer disease reveals a dichotomy of protein turnover. Free Radic Biol Med; in press
Duarte AI, Moreira PI, Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Res; in press
Correia SC, Santos RX, Cardoso SM, Santos MS, Oliveira CR, Moreira PI. Cyanide preconditioning protects brain endothelial and NT2 neuron-like cells against glucotoxicity: Role of mitochondrial reactive oxygen species and HIF-1α. Neurobiol Dis 2012;45:206-218.
Correia SC, Santos RX, Perry G, Zhu X, Moreira PI, Smith MA. Insulin-resistant brain state: the culprit in sporadic Alzheimer’s disease. Ageing Res Rev 2011;10:264-273.
Cardoso S, Santos MS, Seiça R, Moreira PI. Cortical and hippocampal mitochondria bioenergetics and oxidative status during hyperglycemia and/or insulin-induced hypoglycemia. Biochim Biophys Acta 2010;1802:942-951.
Carvalho C, Santos MS, Baldeiras I, Oliveira CR, Seiça R, Moreira PI. Chronic hypoxia potentiates age-related oxidative imbalance in brain vessels and synaptosomes. Curr Neurovasc Res 2010;7:288-300.
Santos RX, Correia SC, Wang X, Perry G, Smith MA, Moreira PI, Zhu X. A synergistic dysfunction of mitochondrial fission/fusion dynamics and mitophagy in Alzheimer’s disease. J Alzheimers Dis 2010;20:S401-412.
Wang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, Casadesus G, Zhu X. Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci USA 2008;105:19318-19323.
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