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| Molecular Mechanisms of Disease |
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PAULA I. MOREIRA, PhD
Domain of Specialization
Mitochondrial dysfunction and oxidative stress in brain aging, Alzheimer’s disease and diabetes.
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| Research Interests |
| We are interested in elucidating the role of mitochondrial-signaling pathways in neuronal and endothelial dysfunction that occur in brain aging, Alzheimer’s disease and diabetes-associated complications. Special attention is given to the crosstalk between mitochondrial- and insulin-signaling pathways. We are also interested in clarifying the potential protective role of hypoxic preconditioning in the above-mentioned pathological conditions. |
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| Research Highlights |
| We provided evidence that mitochondria are a fundamental link between diabetes and AD, two age-related pathologies. Brain mitochondria isolated from diabetic rats have an increased susceptibility to amyloid β injury and mitochondrial dysfunction is exacerbated in older animals. Data obtained with cultured fibroblasts and human brain tissue corroborates the existence of an age-related mitochondrial impairment that is more pronounced in AD. Furthermore, we found that mitochondrial dysfunction in AD is associated with increased degradation of these organelles by autophagy. |
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| Ongoing Projects |
| Exploring the crosstalk between mitochondrial reactive oxygen species and the transcriptional factor hypoxia factor-1 in neuronal and brain endothelial cells; The pathological interaction between diabetes and Alzheimer’s disease: exploring the role of brain endothelial mitochondria and uncoupling proteins. |
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| Group members |
| Cristina Carvalho |
| PhD student of Cellular Biology |
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| Renato X. Santos |
| PhD student of Cellular Biology |
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| Sónia Correia |
| PhD student of Cellular Biology |
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| Susana Cardoso |
| PhD student of Cellular Biology |
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| Patrícia Sousa |
Master student of Medicine
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| Steve Carvalho |
Master student of Biology
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| Collaborations |
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| National |
| Mitochondrial Toxicology and Pharmacology Group - CNBC (Paulo Oliveira); Understanding and treating diabetes and diabetic endothelial dysfunction – IBILI (Raquel Seiça) |
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| International |
| Institute of Pathology, Case Western Reserve University, USA (Mark A. Smith; Xiongwei Zhu); College of Sciences, University of Texas at San Antonio, USA (George Perry) |
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| Curriculum Vitae |
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Professional Activity:
Teaching Assistant at Instituto de Fisiologia, Faculdade de Medicina, Universidade de Coimbra and Researcher at CNBC |
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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:
Correia S., Moreira P.I. (2010) Hypoxia-inducible factor 1: a new hope to counteract neurodegeneration? J. Neurochem. 112, 1-12.
Cardoso S., Correia S., Santos R.X., Carvalho C., Santos M.S., Oliveira C.R., Perry G., Smith M.A., Zhu X., Moreira P.I. (2009) Insulin is a two-edged knife on the brain. J. Alzheimer’s Dis. 18, 483-507.
Wang X., Su B., Siedlak S.L., Moreira P.I., Fujioka H., Wang Y., Casadesus G., Zhu X. (2008) Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc. Natl. Acad. Sci. USA 105, 19318-23.
Moreira P.I., Harris P.L.R., Zhu X., Santos M.S., Oliveira C.R., Smith M.A., Perry G. (2007) Lipoic acid and N-acetyl cysteine decrease mitochondrial-related oxidative stress in Alzheimer disease patient fibroblasts. J. Alzheimer’s Dis. 12, 195-206.
Moreira P.I., Siedlak S.L., Wang X., Santos M.S., Oliveira C.R., Tabaton M., Nunomura A., Szweda L.I., Aliev G., Smith M.A., Zhu X., Perry G. (2007) Autophagocytosis of mitochondria is prominent in Alzheimer disease J. Neuropathol. Exp. Neurol. 66, 525-532.
Moreira P.I., Santos M.S., Sena C., Seiça R., Oliveira C.R. (2005) Insulin protects against amyloid beta-peptide toxicity in brain mitochondria of diabetic rats. Neurobiol. Dis. 18, 628-637.
Moreira P.I., Santos M.S., Moreno A.M., Seica R., Oliveira C.R. (2003) Increased vulnerability of brain mitochondria in diabetic (Goto-Kakizaki) rats with aging and amyloid-beta exposure. Diabetes 52, 1449-1456.
Moreira P.I., Santos M.S., Moreno A., Rego A.C., Oliveira C. (2002) Effect of amyloid beta-peptide on permeability transition pore: a comparative study. J. Neurosci. Res. 69, 257-267.
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