Expanding spectrum of prion diseases
Expanding spectrum of prion diseases
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DOI：
10.1042/etls20200037
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发表时间：
2020-09-01
影响因子：
3.8
通讯作者：
Prusiner, Stanley B.
中科院分区：
文献类型：
--
作者：
Ayers, Jacob, I;Paras, Nick A.;Prusiner, Stanley B.
朊病毒最初是在痒病的研究中发现的，痒病是一种绵羊和山羊的传染性神经退行性疾病（ND），被认为是由慢病毒引起的。一旦痒病传播给啮齿动物，人们发现痒病病原体可以通过核酸修饰程序抵抗灭活。最终，这种新型病原体被证明是一种由209个氨基酸组成的蛋白质，由染色体基因编码。在确定瘙痒病病原体中不存在核酸后，感染性机制提出了一个难题，并消除了一种假设的病毒。随后，发现富含 β 折叠的传染性痒病朊病毒蛋白 (PrPSc) 是由主要为 α 螺旋的细胞朊病毒蛋白 (PrPC) 生成的。新生朊病毒形成的翻译后过程涉及 PrPC 中的模板化构象变化，从而产生 PrPSc 的感染性副本。因此，朊病毒是采用替代构象的蛋白质，它们可以自我繁殖，存在于从酵母到人类的各种生物体中。朊病毒已在阿尔茨海默氏症 (AD) 和帕金森氏症 (PD) 疾病中被发现。 APP 和 α-突触核蛋白基因突变已被证明可导致家族性 AD 和 PD。最近，AD 被发现是一种双朊病毒疾病：A beta 朊病毒和 tau 朊病毒均出现在该 ND 中。越来越多的证据表明，α-突触核蛋白朊病毒是帕金森病、多系统萎缩和路易体痴呆的病因。
Prions were initially discovered in studies of scrapie, a transmissible neurodegenerative disease (ND) of sheep and goats thought to be caused by slow viruses. Once scrapie was transmitted to rodents, it was discovered that the scrapie pathogen resisted inactivation by procedures that modify nucleic acids. Eventually, this novel pathogen proved to be a protein of 209 amino acids, which is encoded by a chromosomal gene. After the absence of a nucleic acid within the scrapie agent was established, the mechanism of infectivity posed a conundrum and eliminated a hypothetical virus. Subsequently, the infectious scrapie prion protein (PrPSc) enriched for beta-sheet was found to be generated from the cellular prion protein (PrPC) that is predominantly alpha-helical. The post-translational process that features in nascent prion formation involves a templated conformational change in PrPC that results in an infectious copy of PrPSc. Thus, prions are proteins that adopt alternative conformations, which are self-propagating and found in organisms ranging from yeast to humans. Prions have been found in both Alzheimer's (AD) and Parkinson's (PD) diseases. Mutations in APP and alpha-synuclein genes have been shown to cause familial AD and PD. Recently, AD was found to be a double prion disorder: both A beta and tau prions feature in this ND. Increasing evidence argues for alpha-synuclein prions as the cause of PD, multiple system atrophy, and Lewy body dementia.