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Cellular prion protein in cell differentiation and protection: control of protein synthesis

Grant number: 08/00390-5
Support Opportunities:Regular Research Grants
Duration: November 01, 2008 - April 30, 2011
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Glaucia Noeli Maroso Hajj
Grantee:Glaucia Noeli Maroso Hajj
Host Institution: Hospital A C Camargo. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil


Prions are the etiological agents of several neurodegenerative diseases of animals and humans. The infectious particle is composed of a protein called scrapie prion PrPsc, which has a normal isoform called cellular prion or PrPc. We described a new ligand for PrPc, Stress Inducible 1 (STI1) protein. PrPc-STI1 binding results in neuritogenesis and protection against cell death, making this interaction important for the development and maintenance of functional neurons. Neuronal processes such as synaptogenesis and synaptic plasticity induced by neurotrophic factors are dependent upon the control of protein translation. STI1 has neurotrophic proprieties and these could involve the translational control. In fact, preliminary results indicate that the treatment of neurons with STI1 induces the synthesis of new proteins in neurons. Furthermore, results show that STI1-induced neuroprotection is dependent upon the PI-3K-AKT-mTOR pathway. The neurotrophic proprieties of STI1 that depend on translational regulation emphasize the importance of a better understanding of the etiology of prion diseases. Also, since some tumors present deregulation of translational control signaling pathways, such as mTOR, the contribution of STI1-PrPc to tumor development will also be evaluated. Other important PrPc interacting molecules are the extracellular matrix (ECM) proteins laminin (Ln) and vitronectin (Vn), being both of these interactions important for neuritogenesis. This project aims to: a) determine if the neurotrophic proprieties of STI1 are dependent on protein synthesis and which are the targets of this regulation; b) determine if integrins can be transmembrane adaptors to PrPc signaling and if PrPc in turn can regulate integrin activity; c) investigate PrPc localization and function in focal adhesions, and correlate these results with cellular migration. We intend to broaden the current knowledge on the mechanisms of prion diseases and possibly suggest new therapeutical approaches. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CAETANO, FABIANA A.; BERALDO, FLAVIO H.; HAJJ, GLAUCIA N. M.; GUIMARAES, ANDRE L.; JUERGENSEN, SOFIA; WASILEWSKA-SAMPAIO, ANA PAULA; HIRATA, PEDRO H. F.; SOUZA, IVANA; MACHADO, CLEITON F.; WONG, DAISY Y. -L.; et al. Amyloid-beta oligomers increase the localization of prion protein at the cell surface. Journal of Neurochemistry, v. 117, n. 3, p. 538-553, . (08/00390-5, 09/14027-2)

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