Inhibition of protease-resistant prion protein accumulation in vitro by curcumin.
Inhibition of the accumulation of protease-resistant prion protein (PrP-res) is a prime strategy in the development of potential transmissible spongiform encephalopathy (TSE) therapeutics. Here we show that curcumin (diferoylmethane), a major component of the spice turmeric, potently inhibits PrP-res accumulation in scrapie agent-infected neuroblastoma cells (50% inhibitory concentration, approximately 10 nM) and partially inhibits the cell-free conversion of PrP to PrP-res. In vivo studies showed that dietary administration of curcumin had no significant effect on the onset of scrapie in hamsters. Nonetheless, other studies have shown that curcumin is nontoxic and can penetrate the brain, properties that give curcumin advantages over inhibitors previously identified as potential prophylactic and/or therapeutic anti-TSE compounds.
Caughey
Byron
B
Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA. bcaughey@nih.gov
Raymond
Lynne D
LD
Raymond
Gregory J
GJ
Maxson
Laura
L
Silveira
Jay
J
Baron
Gerald S
GS
D000818:Animals; D006224:Cricetinae; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D010450:Endopeptidases / Q000378:metabolism; D008647:Mesocricetus; D009447:Neuroblastoma; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000472:pathogenicity; D012608:Scrapie / Q000188:drug therapy / Q000503:physiopathology; D014407:Tumor Cells, Cultured
D018620:PrPSc Proteins; D010450:Endopeptidases; D003474:Curcumin