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Scrapie-like prion protein accumulates in aggresomes of cyclosporin A-treated cells.
- Source :
-
The EMBO journal [EMBO J] 2003 Feb 03; Vol. 22 (3), pp. 404-17. - Publication Year :
- 2003
-
Abstract
- Prion diseases are infectious, sporadic and inherited fatal neurodegenerations that are propagated by an abnormal refolding of the cellular prion protein PrP(C). Which chaperones assist the normal folding of PrP(C) is unknown. The linkage of familial Gerstmann- Sträussler-Scheinker (GSS) syndrome with proline substitutions in PrP raised the prospect that peptidylprolyl cis-trans isomerases (PPIases) may play a role in normal PrP metabolism. Here we used cyclo sporin A (CsA), an immunosuppressant, to inhibit the cyclophilin family of PPIases in cultured cells. CsA-treated cells accumulated proteasome-resistant, 'prion-like' PrP species, which deposited in long-lived aggresomes. PrP aggresomes also formed with disease-linked proline mutants when proteasomes were inhibited. These results suggest mechanisms whereby abnormally folded cytosolic PrP may in some cases participate in the development of spontaneous and inherited prion diseases.
- Subjects :
- Animals
CHO Cells metabolism
CHO Cells ultrastructure
Cricetinae
Cyclosporine metabolism
Cysteine Endopeptidases metabolism
Inclusion Bodies chemistry
Models, Biological
Multienzyme Complexes metabolism
Mutation
PrPC Proteins genetics
PrPSc Proteins metabolism
Proline metabolism
Proteasome Endopeptidase Complex
Protein Folding
Tubulin metabolism
Ubiquitin metabolism
Vimentin metabolism
Cyclosporine pharmacology
Immunosuppressive Agents metabolism
Inclusion Bodies metabolism
PrPC Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 22
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 12554642
- Full Text :
- https://doi.org/10.1093/emboj/cdg045