In multiple system atrophy (MSA), progressive neurodegeneration results from the protein α-synuclein misfolding into a self-templating prion conformation that spreads throughout the brain. MSA prions are transmissible to transgenic (Tg) mice expressing mutated human α-synuclein (TgM83^+/−), inducing neurological disease following intracranial inoculation with brain homogenate from deceased patient samples. Noting the similarities between α-synuclein prions and PrP scrapie (PrP^Sc) prions responsible for Creutzfeldt–Jakob disease (CJD), we investigated MSA transmission under conditions known to result in PrP^Sc transmission. When peripherally exposed to MSA via the peritoneal cavity, hind leg muscle, and tongue, TgM83^+/− mice developed neurological signs accompanied by α-synuclein prions in the brain. Iatrogenic CJD, resulting from PrP^Sc prion adherence to surgical steel instruments, has been investigated by incubating steel sutures in contaminated brain homogenate before implantation into mouse brain. Mice studied using this model for MSA developed disease, whereas wire incubated in control homogenate had no effect on the animals. Notably, formalin fixation did not inactivate α-synuclein prions. Formalin-fixed MSA patient samples also transmitted disease to TgM83^+/− mice, even after incubating in fixative for 244 months. Finally, at least 10% sarkosyl was found to be the concentration necessary to partially inactivate MSA prions. These results demonstrate the robustness of α-synuclein prions to denaturation. Moreover, they establish the parallel characteristics between PrP^Sc and α-synuclein prions, arguing that clinicians should exercise caution when working with materials that might contain α-synuclein prions to prevent disease.

在多系统萎缩症（MSA）中，进行性神经退行性变是由蛋白质α-突触核蛋白错误折叠成可自我模板化的病毒构象引起的，这种构象遍布整个大脑。MSA ions病毒可传播给表达突变的人α-突触核蛋白（TgM83 ^+/-）的转基因（Tg）小鼠，在颅内接种死者患者脑匀浆后诱发神经系统疾病。注意到α-突触核蛋白蛋白与负责克雅氏病（CJD）的PrP瘙痒病（PrP ^Sc）ions蛋白之间的相似性，我们在已知导致PrP ^Sc传播的条件下研究了MSA传播。当通过腹膜腔，后腿肌肉和舌头外周暴露于MSA时，TgM83 ^+/-小鼠在大脑中出现神经系统症状，并伴有α-突触核蛋白pr病毒。由PrP ^Sc pr病毒对外科钢制器械的粘附产生的医源性CJD已通过在植入小鼠脑部之前在受污染的脑匀浆中孵育钢缝线进行了研究。使用该模型对MSA进行研究的小鼠患上了疾病，而在对照匀浆中温育的线对动物没有影响。值得注意的是，福尔马林固定不会使α-突触核蛋白病毒失活。福尔马林固定的MSA患者样品也将疾病传播给TgM83 ^+/-小鼠，即使在固定剂中孵育244个月后也是如此。最后，发现至少10％的鲨鱼糖基是部分灭活MSA pr病毒所必需的浓度。这些结果证明了α-突触核蛋白病毒对变性的鲁棒性。此外，他们建立了PrP ^Sc和α-突触核蛋白蛋白之间的平行特征，认为临床医生在使用可能含有α-突触核蛋白蛋白的材料预防疾病时应谨慎行事。