在固体表面上敏感检测α-synuclein,tau和prion蛋白的病态种子
Christina D Orrú1, Bradley R Groveman1, Andrew G Hughson1
1Laboratory of Neurological Infections and Immunity (LNII), Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
PLoS pathogens
|April 19, 2024
概括
类蛋白质种子 (PrP,α-synuclein,tau) 在钢面上可检测到一年以上,即使在清洗后. 新的表面RT-QuIC测定可以在各种物体上检测这些生物危害,有助于疾病控制.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 病理学 病理学 病理学
背景情况:
- 和类聚合物 (PrP,α-synuclein,tau) 是神经退行性疾病的标志,如CJD,帕金森病和阿尔茨海默病.
- 这些蛋白质聚合物在固体表面的存在构成潜在的生物危害,使污染清除和疾病传播控制复杂化.
- 目前对表面束的子的检测方法,如实时震动诱导转换 (RT-QuIC),需要直接浸泡或转移,限制了它们的应用.
研究的目的:
- 开发和验证高度敏感的基于表面的RT-QuIC协议,用于在固体物体上检测子和子类种子 (α-synuclein,tau,PrP).
- 为了评估这些病态种子在钢表面的稳定性和检测性,随着时间的推移和清洗程序后.
- 建立实用的采样方法,用于检测较大的物体和手术仪器的表面污染.
主要方法:
- 开发了表面RT-QuIC协议,涉及暂时将采样介质应用于含α-synuclein,tau或PrP种子的大脑组织的不同稀释污染的钢表面.
- 在钢丝线上测试了类种子的稳定性,长达一年,包括在酶清洁和杀菌后.
- 评估了测试的灵敏度,使用受子疾病影响的各种物种的大脑组织稀释和受污染的手术仪器样本.
主要成果:
- 类种子 (α-synuclein,tau,PrP) 在钢丝上可检测至少一年,即使在酶清洗和杀菌后也会持续存在.
- 表面RT-QuIC成功检测了在患有Lewy体痴呆症的α-synuclein种子,脑组织在10−6.的稀释下在钢上干燥.
- 在暴露于高度稀释的阿尔茨海默氏症和子疾病影响的大脑组织的钢上检测到tau和prp播种活动,分别 (高达10−8和10−8).
- 来自受子感染的小鼠的受污染的手术仪器在10−6稀释下产生了积极的结果.
- 即使在表面采样和储存后添加复合PrP基质时,对子检测的测试灵敏度也保持不变.
结论:
- 原型表面RT-QuIC协议使得在固体物体上高度敏感地检测病态α-synuclein,tau和PrP种子.
- 这些方法为评估与蛋白质病变相关的表面污染和生物危害提供了一种实用的方法.
- 这些发现对感染控制,仪器灭菌和和类疾病的早期诊断具有重要意义.
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