Bibliographic Details
| Title: |
Cell Type-Specific Neuroprotective Activity of Untranslocated Prion Protein. |
| Authors: |
Restelli, Elena1,2, Fioriti, Luana1,2,3, Mantovani, Susanna1,2, Airaghi, Simona1,2, Forloni, Gianluigi2, Chiesa, Roberto1,2 roberto.chiesa@marionegri.it |
| Source: |
PLoS ONE. 2010, Vol. 5 Issue 10, p1-9. 9p. |
| Subject Terms: |
*PRION diseases, *PROTEINS, *NEUROPROTECTIVE agents, *ENDOPLASMIC reticulum, *BIOCHEMISTRY, *CELLS, *BIOMOLECULES, *PATHOGENIC microorganisms, *CYTOSOL |
| Abstract: |
Background: A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP). However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions. Principal Findings: Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells. Significance: These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function. [ABSTRACT FROM AUTHOR] |
|
Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
