Shaked Gideon M, Engelstein Roni, Avraham Inbal, Kahana Esther, Gabizon Ruth
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, 91120, Jerusalem, Israel.
Brain Res. 2003 Sep 5;983(1-2):137-43. doi: 10.1016/s0006-8993(03)03045-2.
PrP(Sc), an aberrantly folded protein, is the only identified component of the prion, an agent causing fatal neurodegenerative diseases such as scrapie and bovine spongiform encephalopathy. Dimethyl sulfoxide (DMSO) has been shown to reduce the accumulation of PrP(Sc) in scrapie-infected (ScN2a) cells, and to inhibit its aggregation in vitro. In humans, DMSO was used successfully in the treatment of various peripheral amyloidotic diseases. Here we show that administration of DMSO to scrapie-infected hamsters significantly prolonged disease incubation time, as well as delayed the accumulation of PrP(Sc) in Syrian hamster brains. Interestingly, administration of DMSO to scrapie sick hamsters resulted in increased clearance of protease-resistant PrP in their urine. We conclude that although DMSO by itself may not be sufficient to cure prion diseases, it may be considered as a component in a 'cocktail' drug approach for these disorders. Also, urine PrP testing should be considered for the assessment of treatment efficacy.
朊病毒蛋白(Sc型)是一种折叠异常的蛋白质,是唯一已确定的朊病毒组成成分,朊病毒是一种可引发诸如羊瘙痒症和牛海绵状脑病等致命神经退行性疾病的病原体。二甲基亚砜(DMSO)已被证明可减少羊瘙痒症感染(ScN2a)细胞中朊病毒蛋白(Sc型)的积累,并在体外抑制其聚集。在人类中,二甲基亚砜已成功用于治疗各种外周淀粉样变性疾病。在此我们表明,给感染羊瘙痒症的仓鼠施用二甲基亚砜可显著延长疾病潜伏期,并延缓叙利亚仓鼠脑中朊病毒蛋白(Sc型)的积累。有趣的是,给患羊瘙痒症的仓鼠施用二甲基亚砜会使其尿液中抗蛋白酶朊病毒蛋白的清除增加。我们得出结论,虽然二甲基亚砜本身可能不足以治愈朊病毒疾病,但它可被视为针对这些疾病的“鸡尾酒”药物疗法中的一种成分。此外,应考虑通过检测尿液中的朊病毒蛋白来评估治疗效果。