Inhibition of P53-related apoptosis had no effect on PrP(Sc) accumulation and prion disease incubation time.
Results from several laboratories indicate that apoptosis via the P53 pathway is involved in prion disease pathogenesis. Prion diseases, among them scrapie and BSE, are a group of fatal neurodegenerative disorders associated with the conversion of PrP(C) to PrP(Sc), its conformational abnormal isoform. In this work, we tested whether an established anti-apoptotic reagent, PFT, which has been shown in different systems to inhibit P53 activity, can delay the outbreak of prion disease in infected animals. Our findings indicate that although PFT efficiently reduced caspase 3 expression in brains from scrapie sick hamsters, as well as inhibited PrP(Sc) accumulation in cell culture, it had no effect on disease incubation time or PrP(Sc) accumulation in vivo. We conclude that the P53 dependent apoptosis may not be an obligatory mechanism for prion disease-induced cell death.
Engelstein
Roni
R
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem 91120, Israel.
Grigoriadis
Nikolas
N
Greig
Nigel H
NH
Ovadia
Haim
H
Gabizon
Ruth
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D052160:Benzothiazoles; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D004195:Disease Models, Animal; D018450:Disease Progression; D008647:Mesocricetus; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018620:PrPSc Proteins / Q000378:metabolism*; D012608:Scrapie / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013844:Thiazoles / Q000494:pharmacology*; D014050:Toluene / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D052160:Benzothiazoles; D018620:PrPSc Proteins; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases