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The role of prion strain diversity in the development of successful therapeutic treatments.
Progress in Molecular Biology and Translational Science ( IF 4.025 ) Pub Date : 2020-08-28 , DOI: 10.1016/bs.pmbts.2020.07.001
Sara A M Holec 1 , Alyssa J Block 2 , Jason C Bartz 2
Affiliation  

Prions are a self-propagating misfolded conformation of a cellular protein. Prions are found in several eukaryotic organisms with mammalian prion diseases encompassing a wide range of disorders. The first recognized prion disease, the transmissible spongiform encephalopathies (TSEs), affect several species including humans. Alzheimer's disease, synucleinopathies, and tauopathies share a similar mechanism of self-propagation of the prion form of the disease-specific protein reminiscent of the infection process of TSEs. Strain diversity in prion disease is characterized by differences in the phenotype of disease that is hypothesized to be encoded by strain-specific conformations of the prion form of the disease-specific protein. Prion therapeutics that target the prion form of the disease-specific protein can lead to the emergence of drug-resistant strains of prions, consistent with the hypothesis that prion strains exist as a dynamic mixture of a dominant strain in combination with minor substrains. To overcome this obstacle, therapies that reduce or eliminate the template of conversion are efficacious, may reverse neuropathology, and do not result in the emergence of drug resistance. Recent advancements in preclinical diagnosis of prion infection may allow for a combinational approach that treats the prion form and the precursor protein to effectively treat prion diseases.



中文翻译:

朊病毒菌株多样性在成功治疗的发展中的作用。

朊病毒是细胞蛋白质的自我繁殖错误折叠构象。朊病毒存在于几种真核生物中,哺乳动物朊病毒疾病包括多种疾病。第一个公认的朊病毒病,即传染性海绵状脑病 (TSE),影响包括人类在内的多个物种。阿尔茨海默病、突触核蛋白病和 tau 蛋白病具有相似的疾病特异性蛋白朊病毒形式的自我传播机制,让人联想到 TSE 的感染过程。朊病毒疾病的菌株多样性以疾病表型的差异为特征,该表型被假设由疾病特异性蛋白的朊病毒形式的菌株特异性构象编码。针对疾病特异性蛋白质的朊病毒形式的朊病毒疗法可导致耐药性朊病毒菌株的出现,这与朊病毒菌株作为优势菌株与次要亚菌株的动态混合物存在的假设一致。为了克服这一障碍,减少或消除转化模板的疗法是有效的,可以逆转神经病理学,并且不会导致耐药性的出现。朊病毒感染临床前诊断的最新进展可能允许采用治疗朊病毒形式和前体蛋白的组合方法,以有效治疗朊病毒疾病。减少或消除转化模板的疗法是有效的,可以逆转神经病理学,并且不会导致耐药性的出现。朊病毒感染临床前诊断的最新进展可能允许采用治疗朊病毒形式和前体蛋白的组合方法,以有效治疗朊病毒疾病。减少或消除转化模板的疗法是有效的,可以逆转神经病理学,并且不会导致耐药性的出现。朊病毒感染临床前诊断的最新进展可能允许采用治疗朊病毒形式和前体蛋白的组合方法,以有效治疗朊病毒疾病。

更新日期:2020-09-20
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