Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Cambridge, MA, USA.
Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, STROBE, NSF Science and Technology Center, University of California, Los Angeles, Los Angeles, CA, USA.
Curr Opin Neurobiol. 2024 Jun;86:102857. doi: 10.1016/j.conb.2024.102857. Epub 2024 Mar 15.
The concept of 'prion-like' behavior has emerged in the study of diseases involving protein misfolding where fibrillar structures, called amyloids, self-propagate and induce disease in a fashion similar to prions. From a biological standpoint, in order to be considered 'prion-like,' a protein must traverse cells and tissues and further propagate via a templated conformational change. Since 2017, cryo-electron microscopy structures from patient-derived 'prion-like' amyloids, in particular tau, have been presented and revealed structural similarities shared across amyloids. Since 2021, cryo-EM structures from prions of known infectivity have been added to the ex vivo amyloid structure family. In this review, we discuss current proposals for the 'prion-like' mechanisms of spread for tau and prion protein as well as discuss different influencers on structures of aggregates from tauopathies and prion diseases. Lastly, we discuss some of the current hypotheses for what may distinguish structures that are 'prion-like' from transmissible prion structures.
“朊病毒样”行为的概念出现在涉及蛋白质错误折叠的疾病研究中，其中纤维状结构，称为淀粉样蛋白，自我传播并以类似于朊病毒的方式诱导疾病。从生物学的角度来看，为了被认为是“朊病毒样”，蛋白质必须穿越细胞和组织，并通过模板化构象变化进一步传播。自 2017 年以来，已经提出了源自患者的“朊病毒样”淀粉样蛋白（特别是 tau）的冷冻电子显微镜结构，并揭示了淀粉样蛋白之间共享的结构相似性。自 2021 年以来，具有已知传染性的朊病毒的冷冻电镜结构已被添加到体外淀粉样蛋白结构家族中。在这篇综述中，我们讨论了 tau 和朊病毒蛋白传播的“朊病毒样”机制的当前建议，并讨论了影响tau 病和朊病毒病中聚集物结构的不同因素。最后，我们讨论了一些当前的假设，这些假设可能区分具有“朊病毒样”特征的结构与可传播的朊病毒结构。
