Beyond Amyloid Fibers: Accumulation, Biological Relevance, and Regulation of Higher-Order Prion Architectures.

Beyond Amyloid Fibers: Accumulation, Biological Relevance, and Regulation of Higher-Order Prion Architectures.
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DOI:
10.3390/v14081635
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发表时间:
2022-07-27
期刊:
Viruses
影响因子:
--
通讯作者:
--
中科院分区:
其他
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淀粉样纤维的形成与多种疾病和表型状态有关。这些淀粉样纤维在体内和体外通常组装成多原纤维的高级结构。朊病毒在酵母中的繁殖,淀粉样蛋白为基础的过程,是一个有吸引力的模型,探索这些聚集状态和淀粉样蛋白动力学的生物后果之间的联系。在这里,我们整合了当前的知识状态,突出了进一步洞察的机会,并与体外更复杂的系统进行了比较。有证据表明,高阶原纤维结构存在于离体疾病相关环境和酵母体内允许条件下,包括但不限于导致朊病毒形成或不稳定的那些。然而,这些后者淀粉样蛋白结构的生物学意义或它们如何被调节,由于不一致的实验条件和分析方法而变得复杂,尽管可能涉及Hsp 70伴侣蛋白Ssa 1/2。组装状态之间的转换可以形成一个机械的基础,以解释一些混淆的意见,周围的朊病毒监管,但有限的缺乏统一的方法来生物药理学比较这些组装状态。未来令人兴奋的实验入口可能会提供进一步深入了解的机会。
The formation of amyloid fibers is associated with a diverse range of disease and phenotypic states. These amyloid fibers often assemble into multi-protofibril, high-order architectures in vivo and in vitro. Prion propagation in yeast, an amyloid-based process, represents an attractive model to explore the link between these aggregation states and the biological consequences of amyloid dynamics. Here, we integrate the current state of knowledge, highlight opportunities for further insight, and draw parallels to more complex systems in vitro. Evidence suggests that high-order fibril architectures are present ex vivo from disease relevant environments and under permissive conditions in vivo in yeast, including but not limited to those leading to prion formation or instability. The biological significance of these latter amyloid architectures or how they may be regulated is, however, complicated by inconsistent experimental conditions and analytical methods, although the Hsp70 chaperone Ssa1/2 is likely involved. Transition between assembly states could form a mechanistic basis to explain some confounding observations surrounding prion regulation but is limited by a lack of unified methodology to biophysically compare these assembly states. Future exciting experimental entryways may offer opportunities for further insight.
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