Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, 128 00 Prague, Czech Republic.
Molecules. 2022 Jan 18;27(3):611. doi: 10.3390/molecules27030611.
Prion disorders, or transmissible spongiform encephalophaties (TSE), are fatal neurodegenerative diseases affecting mammals. Prion-infectious particles comprise of misfolded pathological prion proteins (PrP). Different TSEs are associated with distinct PrP folds called prion strains. The high resistance of prions to conventional sterilization increases the risk of prion transmission in medical, veterinary and food industry practices. Recently, we have demonstrated the ability of disulfonated hydroxyaluminum phthalocyanine to photodynamically inactivate mouse RML prions by generated singlet oxygen. Herein, we studied the efficiency of three phthalocyanine derivatives in photodynamic treatment of seven mouse adapted prion strains originating from sheep, human, and cow species. We report the different susceptibilities of the strains to photodynamic oxidative elimination of PrP epitopes: RML, A139, Fu-1 > mBSE, mvCJD > ME7, 22L. The efficiency of the phthalocyanine derivatives in the epitope elimination also differed (AlPcOH(SO) > ZnPc(SO) > SiPc(OH)(SO)) and was not correlated to the yields of generated singlet oxygen. Our data suggest that the structural properties of both the phthalocyanine and the PrP strain may affect the effectiveness of the photodynamic prion inactivation. Our finding provides a new option for the discrimination of prion strains and highlights the necessity of utilizing range of prion strains when validating the photodynamic prion decontamination procedures.
朊病毒疾病，或传染性海绵状脑病（TSE），是影响哺乳动物的致命神经退行性疾病。朊病毒感染性颗粒由错误折叠的病理性朊病毒蛋白（PrP）组成。不同的 TSE 与不同的 PrP 折叠相关，称为朊病毒株。朊病毒对常规消毒的高度抗性增加了在医学、兽医和食品工业实践中朊病毒传播的风险。最近，我们已经证明二磺化羟基铝酞菁能够通过生成单线态氧来光动力失活小鼠 RML 朊病毒。在此，我们研究了三种酞菁衍生物在七种源自绵羊、人类和牛种的适应小鼠的朊病毒株的光动力治疗中的效率。我们报告了这些株对 PrP 表位的光动力氧化消除的不同敏感性：RML、A139、Fu-1 > mBSE、mvCJD > ME7、22L。酞菁衍生物在消除表位方面的效率也不同（AlPcOH（SO）> ZnPc（SO）> SiPc（OH）（SO）），并且与生成的单线态氧的产率无关。我们的数据表明，酞菁和朊病毒株的结构特性都可能影响光动力朊病毒失活的效果。我们的发现为朊病毒株的鉴别提供了一种新的选择，并强调在验证光动力朊病毒去污程序时需要利用多种朊病毒株。
