Maria E. Figueiredo-Pereira, Professor of Biology
Lab Web Site http://pereira.bioweb.hunter.cuny.edu
- Postdoc. 1987-1989, Mount Sinai School Medicine of CUNY
- Ph.D. 1985, New York University
- Postdoc 1985-1986, Population Council @ Rockefeller University
- B.Sc.1970, M.Sc. 1972, University of Lisbon, Portugal
- Role of the ubiquitin/proteasome pathway and inflammation in NEURODEGENERATION
The research in our laboratory investigates mechanisms involved in neuronal degeneration. We specifically focus on mechanisms affected by impairment of the ubiquitin/proteasome pathway (UPP) and inflammation, as it is well established that most neurodegenerative disorders are characterized by two related pathological hallmarks:
(1) the accumulation of ubiquitinated proteins in disease specific neuronal inclusions, and
(2) signs of chronic neuroinflammation, such as gliosis, at the sites of neuronal damage.
Due to the widespread development of these two pathological hallmarks, the outcome of our research is clearly relevant to the prevention and/or treatment of most neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and Huntington’s diseases as well as amyotrophic lateral sclerosis.
One of the major roles of the UPP is to degrade ubiquitinated proteins, thus the neuronal accumulation of the latter is indicative of UPP malfunction. Notably, aging is associated with a decrease in proteasome activity. This supports the view that aging-dependent proteasome impairment is critical to the late onset of both familial and sporadic forms of neurodegenerative disorders. Furthermore, other conditions such as inflammation may affect proteasome activity and exacerbate the neurodegenerative process. In order to develop therapeutic strategies based on proteasome impairment it is critical to tease out which of the proteasome-affected mechanisms are involved in neurodegeneration.
To investigate the mechanisms affected by proteasome impairment we are using proteasome inhibitors and proteasome mutations that impair proteasome activity. Furthermore, we are investigating the effect of a product of inflammation, prostaglandin J2 (PGJ2), shown by our laboratory to be neurotoxic and to induce the accumulation of ubiquitinated proteins.
- Huang Q, Figueiredo-Pereira ME. (2010) “Ubiquitin/proteasome pathway impairment in neurodegeneration: therapeutic implications.” Apoptosis. Feb 4.
- Metcalfe MJ, Figueiredo-Pereira ME.(2010) Relationship between tau pathology and neuroinflammation in Alzheimer's disease. Mt Sinai J Med. Jan;77(1):50-8. Review.PMID: 20101714
- Pierre SR, Lemmens MA, Figueiredo-Pereira ME (2009) Subchronic infusion of the product of inflammation prostaglandin J2 models sporadic Parkinson's disease in mice. J Neuroinflammation. Jul 25;6:18.PMID: 19630993
- Arnaud LT, Myeku N, Figueiredo-Pereira ME (2009). Proteasome-caspase-cathepsin sequence leading to tau pathology induced by prostaglandin J2 in neuronal cells. J Neurochem. Jul;110(1):328-42.
- Talamagas AA, Efthimiopoulos S, Tsilibary EC, Figueiredo-Pereira ME, Tzinia AK.(2007) Abeta(1-40)-induced secretion of matrix metalloproteinase-9 results in sAPPalpha release by association with cell surface APP Neurobiol Dis. Dec;28(3):304-15.
- .Vernace VA, Schmidt-Glenewinkel T, Figueiredo-Pereira ME (2007) Aging and regulated protein degradation: who has the UPPer hand? Aging Cell. Oct;6(5):599-606
- Vernace VA, Arnaud L, Schmidt-Glenewinkel T, Figueiredo-Pereira ME (2007) Aging perturbs 26S proteasome assembly in Drosophila melanogaster. FASEB J. Sep;21(11):2672-82.
- Arnaud L, Robakis NK, Figueiredo-Pereira ME.(2006) It may take inflammation, phosphorylation and ubiquitination to 'tangle' in Alzheimer's disease. Neurodegener Dis. 3(6):313-9.
- Ogburn KD, Figueiredo-Pereira ME. (2006) Cytoskeleton/endoplasmic reticulum collapse induced by prostaglandin J2 parallels centrosomal deposition of ubiquitinated protein aggregates. J Biol Chem. Aug 11;281(32):23274-84
- Wang Z, Aris VM, Ogburn KD, Soteropoulos P, Figueiredo-Pereira ME. (2006) Prostaglandin J2 alters pro-survival and pro-death gene expression patterns and 26 S proteasome assembly in human neuroblastoma cells. J Biol Chem. Jul 28;281(30):21377-86
- Ogburn, K., Bottiglieri, T., Wang, Z. and Figueiredo-Pereira, M.E. (2005) "Prostaglandin J2 reduces catechol-o-methyl transferase activity and enhances dopamine toxicity in neuronal cells" Neurobiol. Dis. May;22(2):294-301
- Wang, Z. and Figueiredo-Pereira, M.E. (2005) "Inhibition of sequestosome 1/p62 up-regulation prevents aggregation of ubiquitinated proteins induced by prostaglandin J2 without reducing its neurotoxicity" Mol. Cell. Neurosci. 29: 222-31
- Li, Z., Jansen, M., Ogburn, K., Salvatierra, L, Hunter, L.and Figueiredo-Pereira, M.E. (2004) "The neurotoxic prostaglandin J2 enhances cyclooxygenase-2 expression in neuronal cells through the p38MAPK pathway: a death wish?" J. Neuroscience Res. 78: 824-36
- Li, Z., Arnaud, L., Rockwell, P. and Figueiredo-Pereira, M.E. (2004) "A single amino acid substitution in a proteasome subunit triggers aggregation of ubiquitinated proteins in stressed neuronal cells" J. Neurochem. 90 (1): 19-28.
- Li, Z., Melandri, F., Berdo, I., Jansen, M., Hunter, L., Wright, S., Valbrun, D., and Figueiredo-Pereira, M.E. (2004) " 12-Prostaglandin J2 inhibits the ubiquitin hydrolase UCH-L1 and elicits ubiquitin-protein aggregation without proteasome inhibition" Biochem. Biophys. Res. Commun. 319: 1171-80
Sites of Interest: