Pushing the limits in single particle cryo-EM: general discussion.
Pushing the limits in single particle cryo-EM: general discussion.
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突破单粒子冷冻电镜的极限：一般讨论。
DOI：
10.1039/d2fd90063g
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发表时间：
2022
影响因子：
3.4
通讯作者：
Bakker SE
中科院分区：
文献类型：
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作者：
Bakker SE
sors HW Scheres回答说：我真的不知道，但至少我希望动物模型能产生与我们在疾病中观察到的悲叹结构。我们目前正致力于使小鼠（过度）表达人类tau蛋白的截断版本。ren<s:1>·AW·弗兰克评论道：太棒了，你已经成功地利用截短的tau蛋白确定了产生哀叹的条件，这些哀叹的结构与离体死后阿尔茨海默病（AD）脑组织的结构高度相似（https://doi）。org/10.1039/d2fd00034b)。这是否意味着tau蛋白生长的“种子”是由AD脑组织中截断的tau蛋白形成的，可能是通过蛋白质水解形成的？接着，这些体外制备的tau（具有疾病相关结构）是否能够在体外播种由全长tau组成的相同疾病相关结构？同样，体外制备的tau哀叹（具有疾病相关结构）是否能够在转基因野生型tau表达小鼠的大脑中传播/传播？
Sjors HW Scheres answered: I don’t really know, but at the very least I would like the animal model to produce the same lament structures as we’ve observed in disease. We’re currently working on making mice that (over) express truncated versions of human tau.René AW Frank remarked: Brilliant that you have managed to identify conditions using truncated tau that generate laments with structures that are highly similar to those from ex vivo post-mortem Alzheimer’s disease (AD) brain tissue (https://doi. org/10.1039/d2fd00034b). Could this imply that the ‘seeds’ for tau lament growth are formed of truncated tau in AD brain tissue, perhaps by proteolysis? Following on from this, are these in vitro-prepared tau laments (with disease-relevant structure) capable of seeding the same disease-relevant structure composed of full-length tau in vitro? Similarly, are the in vitro-prepared tau laments (with disease-relevant structure) capable of transmission/spread in the brains of transgenic wild-type tau-expressing mice?