Details

Autor(en) / Beteiligte

• Bate, Clive
• Reid, Stuart
• Williams, Alun

Titel

Phospholipase A2 Inhibitors or Platelet-activating Factor Antagonists Prevent Prion Replication

Ist Teil von

• The Journal of biological chemistry, 2004-08, Vol.279 (35), p.36405-36411

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• A key feature of prion diseases is the conversion of the cellular prion protein (PrP C ) into disease-related isoforms (PrP Sc ), the deposition of which is thought to lead to neurodegeneration. In this study a pharmacological approach was used to determine the metabolic pathways involved in the formation of protease-resistant PrP (PrP res ) in three prion-infected cell lines (ScN2a, SMB, and ScGT1 cells). Daily treatment of these cells with phospholipase A 2 (PLA 2 ) inhibitors for 7 days prevented the accumulation of PrP res . Glucocorticoids with anti-PLA 2 activity also prevented the formation of PrP res and reduced the infectivity of SMB cells. Treatment with platelet-activating factor (PAF) antagonists also reduced the PrP res content of cells, while the addition of PAF reversed the inhibitory effect of PLA 2 inhibitors on PrP res formation. ScGT1 cells treated with PLA 2 inhibitors or PAF antagonists for 7 days remained clear of detectable PrPres when grown in control medium for a further 12 weeks. Treatment of non-infected cells with PLA 2 inhibitors or PAF antagonists reduced PrP C levels suggesting that limiting cellular PrP C may restrict prion formation in infected cells. These data indicate a pivotal role for PLA 2 and PAF in controlling PrP res formation and identify them as potential therapeutic agents.