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Mitochondrial Dysfunction and Signaling in Neurodegeneration Group

 
Selective neurodegeneration in irreversible disorders of the CNS has been largely attributed to mitochondrial impairment and protein misfolding. However, how modified or mutant proteins interfere with mitochondria is not clear. The main objective of our group is to determine defective intracellular mechanisms and identify molecular targets for therapeutic intervention underlying mitochondrial dysfunction and cell death in distinct neurodegenerative conditions, namely polyglutamine expansion (Huntington’s (HD) and Machado-Joseph’s (MJD) disorders), Parkinson’s (PD) and Alzheimer’s (AD) diseases, and in the neuropathology caused by drug addiction. We also aim to evaluate the efficacy of neuroprotective strategies (pharmacological and cell replacement therapies) that help recovering mitochondrial function and thus neuronal survival. Thus, the group is also interested in the use of genetically-modified mice neural stem cells as a tool for brain repair. 
 

 
 
Present and Former Funding
 
          Fundação para a Ciência e a Tecnologia (FCT), Portugal
       
        High Q Foundation (New York, USA)
    
        Instituto de Investigação Interdisciplinar (III) – University of Coimbra
       
        Faculty of Medicine (FMED) – University of Coimbra
 
 
 
 
 

   Recent publications

  • Rosenstock T. R., de Brito O. M., Lombardi V., Louros S., Ribeiro M., Almeida S., Ferreira I. L., Oliveira C. R., Rego A. C. (2011) FK506 ameliorates cell death features in Huntington's disease striatal cell models. Neurochem Int. 59:600-9.

  • Ferreira I. L., Cunha-Oliveira T., Nascimento M. V., Ribeiro M., Proença M. T., Januário C., Oliveira C. R., Rego A. C. (2011) Bioenergetic dysfunction in Huntington's disease human cybrids. Exp Neurol.  231, 127-34.
  • Cunha-Oliveira T., Rego A. C., Garrido J., Borges F., Macedo T., Oliveira C. R. (2010) Neurotoxicity of heroin-cocaine combinations in rat cortical neurons. Toxicology. 276, 11-7.
  • Ferreira I. L., Nascimento M. V., Ribeiro M., Almeida S., Cardoso S. M., Grazina M., Pratas J., Santos M. J., Januário C., Oliveira C. R., Rego A. C.  (2010) Mitochondrial-dependent apoptosis in Huntington's disease human cybrids. Exp Neurol. 222, 243-55.
  • Almeida S., Cunha-Oliveira T., Laço M., Oliveira C. R., Rego A.C. (2010) Dysregulation of CREB activation and histone acetylation in 3-nitropropionic acid-treated cortical neurons: prevention by BDNF and NGF. Neurotox Res. 17, 399-405.
  • Almeida S., Laço M., Cunha-Oliveira T., Oliveira C. R. , Rego A. C. (2009) BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons. Neurobiol Dis. 35, 448-56.
  • Silva A., Pereira J., Oliveira C. R., Relvas J. B., Rego A. C.(2009) BDNF and extracellular matrix regulate differentiation of mice neurosphere-derived cells into a GABAergic neuronal phenotype.J Neurosci Res. 87, 1986-96.
  • Almeida S., Sarmento-Ribeiro A. B., Januário C., Rego A. C., Oliveira C. R. (2008) Evidence of apoptosis and mitochondrial abnormalities in peripheral blood cells of Huntington's disease patients. Biochem. Biophys. Res. Commun. 374, 599-603. 
  • Duarte A. I., Santos P., Oliveira C. R., Santos M. S., Rego A. C. (2008) Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3beta signalling pathways and changes in protein expression. Biochim. Biophys. Acta - Mol. Cell Res. 1783, 994-1002. 
  • Ferreiro E., Eufrásio A., Pereira C., Oliveira C. R., Rego A. C. (2007) Bcl-2 overexpression protects against amyloid-beta and prion toxicity in GT1-7 neural cells. J. Alzheimers Dis. 12, 223-228. 
  • Domingues A., Almeida S., da Cruz e Silva E. F., Oliveira C. R., Rego A. C. (2007) Toxicity of beta-amyloid in HEK293 cells expressing NR1/NR2A or NR1/NR2B N-methyl-D-aspartate receptor subunits. Neurochem. Int. 50, 872-880. 
  • Oliveira J. M., Jekabsons M. B., Chen S., Lin A., Rego A. C., Gonçalves J., Ellerby L. M., Nicholls D. G. (2007) Mitochondrial dysfunction in Huntington’s disease: the bioenergetics of isolated and in situ mitochondria from transgenic mice. J. Neurochem. 101, 241-249. 
  • Cunha-Oliveira T., Rego A. C., Garrido J., Borges F., Macedo T., Oliveira C. R. (2007) Street heroiinduces mitochondrial dysfunction and apoptosis in rat cortical neurons. J. Neurochem. 101, 543-554.
  • Perfeito R, Pereira J, Oliveira CR, Relvas JB, Rego AC. (2007) Trolox Protection of Myelin Membrane in Hydrogen Peroxide-treated mature Oligodendrocytes. Free Radical Research, 41 (4): 444-451. Erratum in: Free Radic Res. 2007 Jun;41(6):738-9
  • Oliveira J. M. A., Chen S., Almeida S., Riley R., Gonçalves J., Oliveira C. R., Hayden M. R., Nicholls D. G., Ellerby L. M., Rego A. C. (2006) Mitochondrial-dependent Ca2+-handling in Huntington’s disease striatal cells: Effect of HDAC inhibitors. J. Neurosci. 26, 11174 –11186. 
  • Duarte A. I., Proença T., Oliveira C. R., Santos M. S., Rego A. C. (2006) Insulin restores metabolic function in cultured cortical neurons subjected to oxidative stress. Diabetes 55, 2863-2870. 
  • Duarte A. I., Santos M. S., Oliveira C. R., Rego A. C. (2005) Insulin neuroprotection against oxidative stress in cortical neurons – involvement of uric acid and glutathione antioxidant defenses. Free Radic. Bio. Med. 39, 876-889. 
  • Almeida S., Domingues A., Rodrigues L., Oliveira C. R., Rego A. C. (2004) FK506 prevents mitochondrial-dependent apoptotic cell death induced by 3-nitropropionic acid in rat primary cortical cultures. Neurobiol. Dis. 17, 435-444.