Cell type-specific neuroprotective activity of untranslocated prion protein

Restelli, Elena, Fioriti, Luana, Mantovani, Susanna, Airaghi, Simona, Forloni, Gianluigi and Chiesa, Roberto (2010) Cell type-specific neuroprotective activity of untranslocated prion protein. PLoS One, 5 10: 1-9. doi:10.1371/journal.pone.0013725

Author Restelli, Elena
Fioriti, Luana
Mantovani, Susanna
Airaghi, Simona
Forloni, Gianluigi
Chiesa, Roberto
Title Cell type-specific neuroprotective activity of untranslocated prion protein
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2010-10-28
Sub-type Article (original research)
DOI 10.1371/journal.pone.0013725
Open Access Status DOI
Volume 5
Issue 10
Start page 1
End page 9
Total pages 9
Place of publication San Francisco, United States
Publisher Public Library of Science
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article # e13725

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 30 Jan 2015, 10:35:30 EST by Susanna Mantovani on behalf of School of Biomedical Sciences