Prion protein lacks robust cytoprotective activity in cultured cells

• Main Authors: Harris David A, Christensen Heather M
• Format: Article
• Language: English
• Published: BMC 2008-08-01
• Series: Molecular Neurodegeneration
• Online Access: http://www.molecularneurodegeneration.com/content/3/1/11

<p>Abstract</p> <p>Background</p> <p>The physiological function of the cellular prion protein (PrP^C) remains unknown. However, PrP^Chas been reported to possess a cytoprotective activity that prevents death of neurons and other cells after a toxic stimulus. To explore this effect further, we attempted to reproduce several of the assays in which a protective activity of PrP had been previously demonstrated in mammalian cells.</p> <p>Results</p> <p>In the first set of experiments, we found that PrP over-expression had a minimal effect on the death of MCF-7 breast carcinoma cells treated with TNF-α and <it>Prn-p</it>^{<it>0/0 </it>}immortalized hippocampal neurons (HpL3-4 cells) subjected to serum deprivation. In the second set of assays, we observed only a small difference in viability between cerebellar granule neurons cultured from PrP-null and control mice in response to activation of endogenous or exogenous Bax.</p> <p>Conclusion</p> <p>Taken together, our results suggest either that cytoprotection is not a physiologically relevant activity of PrP^C, or that PrP^C-dependent protective pathways operative <it>in vivo </it>are not adequately modeled by these cell culture systems. We suggest that cell systems capable of mimicking the neurotoxic effects produced in transgenic mice by N-terminally deleted forms of PrP or Doppel may represent more useful tools for analyzing the cytoprotective function of PrP^C.</p>