The prototype of transmissible neurodegenerative proteinopathies is prion diseases, characterized by aggregation of abnormally folded conformers of the native prion protein. A wealth of mechanisms has been proposed to explain the conformational conversion from physiological protein into misfolded, pathological form, mode of toxicity, propagation from cell‐to‐cell and regional spread. There is increasing evidence that other neurodegenerative diseases, most notably Alzheimer’s disease (Aβ and tau), Parkinson’s disease (α‐synuclein), frontotemporal dementia (TDP43, tau or FUS) and motor neurone disease (TDP43), exhibit at least some of the misfolded prion protein properties. In this review, we will discuss to what extent each of the properties of misfolded prion protein is known to occur for Aβ, tau, α‐synuclein and TDP43, with particular focus on self‐propagation through seeding, conformational strains, selective cellular and regional vulnerability, stability and resistance to inactivation, oligomers, toxicity and summarize the most recent literature on transmissibility of neurodegenerative disorders.

中文翻译：

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朊病毒样机制在神经退行性疾病中的作用

传染性神经退行性蛋白质病的原型是朊病毒病，其特征是天然朊病毒蛋白异常折叠构象异构体的聚集。人们提出了多种机制来解释从生理蛋白质到错误折叠的病理形式的构象转变、毒性模式、细胞间传播和区域扩散。越来越多的证据表明，其他神经退行性疾病，尤其是阿尔茨海默病（Aβ 和 tau）、帕金森病（α-突触核蛋白）、额颞叶痴呆（TDP43、tau 或 FUS）和运动神经元病（TDP43）至少表现出一些错误折叠的朊病毒蛋白特性。在这篇综述中，我们将讨论 Aβ、tau、α-突触核蛋白和 TDP43 中已知的错误折叠朊病毒蛋白的每种特性在多大程度上发生，特别关注通过播种、构象菌株、选择性细胞和区域性的自我繁殖。脆弱性、稳定性和对失活、寡聚物、毒性的抵抗力，并总结了有关神经退行性疾病传播性的最新文献。