摘要
背景:阿尔茨海默病(AD)的发病机制并不是由老年斑的存在直接引起的,而是由有毒的可溶性寡聚物对神经元细胞产生的有害影响引起的。这些物种是在Aβ1-42肽聚集过程中早期形成的,也可以从成熟的原纤维中释放出来。目前,对于早期诊断的有效工具,以及针对AD患者样本中有害物质的药物治疗,仍然缺乏。 目的:通过整合体外免疫化学分析和体内神经元毒性模型,我们的目的是了解和靶向驱动AD毒性的原理。 方法:我们评估了A11和OC构象抗体的特异性和敏感性,以靶向一系列病理相关的淀粉样蛋白构象,并在神经元培养模型中使用一些细胞读数来挽救它们的细胞毒性作用。 结果:我们证明了构象抗体的特殊能力,以标记病理相关的Aβ1-42寡聚物和原纤维,并防止其对神经元细胞的有害影响。 结论:我们的研究结果极大地提高了我们对毒性组装体在神经退行性疾病中的作用的认识,从而为AD提供了新的和更有效的诊断和治疗工具。
关键词: 构象敏感抗体,淀粉样β肽,有毒低聚物,淀粉样原纤维,阿尔茨海默病,蛋白质聚集。
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