In this pair of review articles, Creekmore et al describe the advanced state of cryogenic electron microscopy (cryo-EM) technology, which allows near-atomic level structural resolution, and they outline the role that cryo-EM has played in neurodegenerative disease research. They review progress in understanding intimate structural details of aggregated tau, A-β, α-synuclein, and TDP-43, and how they differ among diseases. They also describe the insights that cryo-EM has provided into the structure of the 26S proteasome and other proteostasis-related factors, including VCP and C9orf72. They include an excellent discussion of the pathophysiology of protein aggregation disorders in the context of what has been learned about cellular proteostatic machinery, and suggest that proteostasis factors may serve as potential therapeutic targets.

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在这对评论文章中，Creekmore 等人描述了低温电子显微镜 (cryo-EM) 技术的先进状态，该技术允许近原子级结构分辨率，并概述了低温 EM 在神经退行性疾病研究中的作用。他们回顾了在理解聚合 tau、A-β、α-突触核蛋白和 TDP-43 的内部结构细节方面的进展，以及它们在疾病之间的差异。他们还描述了冷冻电镜对 26S 蛋白酶体结构和其他蛋白稳态相关因素（包括 VCP 和 C9orf72）的见解。它们包括在所了解的细胞蛋白质稳态机制的背景下对蛋白质聚集障碍的病理生理学的精彩讨论，并建议蛋白质稳态因子可作为潜在的治疗靶点。