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Signs of cross-seeding: aortic medin amyloid as a trigger for protein AA deposition.

机译:交叉播种的迹象:主动脉medin淀粉样蛋白触发蛋白质AA沉积。

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摘要

The highly diverse deposition pattern displayed by systemic amyloidoses, sometimes within the same amyloid disease, remains unexplained. The localized medin (AMed) amyloidosis develops from the precursor protein lactadherin and deposits in the media of the thoracic aorta in almost all individuals above 50 years of age. Given its high prevalence in the population, and the fact that systemic amyloidoses also deposit in the aorta, led us to investigate whether AMed amyloid could influence the tissue distribution of serum amyloid A derived (AA) amyloidosis. Seven aortas from patients with diagnosed systemic AA amyloidosis were investigated. Four displayed partial co-localization between medin and AA aggregates when examined with double-labeling immunofluorescence. Furthermore, in vitro studies showed that AMed amyloid-like fibrils promote the aggregation of protein AA into fibrils. The findings indicate that the highly frequent "senile" amyloidoses may have the potential to initiate fibril formation of the more uncommon amyloidoses by a cross-seeding mechanism.
机译:全身性淀粉样蛋白显示的高度多样化的沉积模式(有时在同一淀粉样蛋白疾病内)仍然无法解释。局部性麦丁(AMed)淀粉样变性病是由前体蛋白乳粘附素形成的,并沉积在几乎所有50岁以上的人的胸主动脉介质中。鉴于其在人群中的患病率很高,而且全身性淀粉样蛋白也沉积在主动脉中,这一事实促使我们研究AMed淀粉样蛋白是否会影响血清淀粉样蛋白A衍生(AA)淀粉样变性的组织分布。研究了来自诊断为系统性AA淀粉样变性病患者的七个主动脉。当用双重标记免疫荧光检查时,四个在medin和AA聚集体之间显示部分共定位。此外,体外研究表明,AMed淀粉样蛋白原纤维可促进蛋白质AA聚集到原纤维中。这些发现表明,高频率的“老年”淀粉样糖可能具有通过交叉播种机制引发较不常见的淀粉样糖原纤维形成的潜力。

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