Oligodendrocytes are susceptible to apoptotic cell death induced by prion protein-derived peptides
✍ Scribed by Isabelle Sponne; Alexandre Fifre; Violette Koziel; Badreddine Kriem; Thierry Oster; Jean-Luc Olivier; Thierry Pillot
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 384 KB
- Volume
- 47
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
Abstract
Neurodegenerative prion diseases, characterized by a progressive dementia, are associated with the accumulation of abnormal forms of the prion (PrP^c^) protein, potentially due to an aberrant regulation of PrP^c^ biogenesis and/or topology. One of these forms, termed ^ctm^PrP, displays a transmembrane conformation and might trigger neuronal cell death in Gerstmann‐Straüssler‐Scheinker (GSS) syndrome and other prion‐associated diseases in humans. Although the primary target cells involved in the progression of prion diseases remain unidentified, it was recently suggested that modifications of the oligodendroglial cells occur early in prion diseases. In the present study, we demonstrate that a putative transmembrane domain of the human PrP^c^, i.e., amino acids 118–135, induces oligodendrocyte (OLG) death in vitro in a time‐ and dose‐dependent manner. The process leading to OLG death and induced by the PrP[118–135] peptide was characterized by DNA fragmentation, cytoskeletal disruption, and caspase activation. Protection against the PrP[118–135] peptide‐induced OLG apoptosis by several antioxidant molecules, such as probucol, propylgallate, and promethazine, suggests that oxidative injuries contribute to the PrP[118–135] cytotoxicity to OLGs. These results suggest a potential pathophysiological role of the ^ctm^PrP‐ and/or PrP fragment‐mediated OLG cytotoxicity in spongiform encephalopathies. © 2004 Wiley‐Liss, Inc.