In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 107, No. 29 ( 2010-07-20), p. 13147-13152
Abstract:
Transmissible spongiform encephalopathies are fatal neurodegenerative diseases caused by the conversion of prion protein (PrP C ) into an infectious isoform (PrP Sc ). How this event leads to pathology is not fully understood. Here we demonstrate that protein synthesis in neurons is enhanced via PrP C interaction with stress-inducible protein 1 (STI1). We also show that neuroprotection and neuritogenesis mediated by PrP C –STI1 engagement are dependent upon the increased protein synthesis mediated by PI3K-mTOR signaling. Strikingly, the translational stimulation mediated by PrP C –STI1 binding is corrupted in neuronal cell lines persistently infected with PrP Sc , as well as in primary cultured hippocampal neurons acutely exposed to PrP Sc . Consistent with this, high levels of eukaryotic translation initiation factor 2α (eIF2α) phosphorylation were found in PrP Sc -infected cells and in neurons acutely exposed to PrP Sc . These data indicate that modulation of protein synthesis is critical for PrP C –STI1 neurotrophic functions, and point to the impairment of this process during PrP Sc infection as a possible contributor to neurodegeneration.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1000784107
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2010
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
Permalink