甲状腺素运载蛋白与β-淀粉样肽的结合——对β-淀粉样肽纤维形成及毒性的影响

Transthyretin binding to A-Beta peptide--impact on A-Beta fibrillogenesis and toxicity.

作者信息

Costa R, Gonçalves A, Saraiva M J, Cardoso I

机构信息

Molecular Neurobiology Unit, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.

出版信息

FEBS Lett. 2008 Mar 19;582(6):936-42. doi: 10.1016/j.febslet.2008.02.034. Epub 2008 Feb 22.

DOI:10.1016/j.febslet.2008.02.034

PMID:18295603

Abstract

It has been suggested that transthyretin (TTR) is involved in preventing A-Beta fibrillization in Alzheimer's disease (AD). Here, we characterized the TTR/A-Beta interaction by competition binding assays. TTR binds to different A-Beta peptide species: soluble (Kd, 28 nM), oligomers and fibrils; diverse TTR variants bind differentially to A-Beta. Transmission electron microscopy (TEM) analysis demonstrated that TTR is capable of interfering with A-Beta fibrillization by both inhibiting and disrupting fibril formation. Co-incubation of the two molecules resulted in the abolishment of A-Beta toxicity. Our results confirmed TTR as an A-Beta ligand and indicated the inhibition/disruption of A-Beta fibrils as a possible mechanism underlying the protective role of TTR in AD.

摘要

有人提出，转甲状腺素蛋白（TTR）参与预防阿尔茨海默病（AD）中的β-淀粉样蛋白纤维化。在此，我们通过竞争结合试验对TTR/β-淀粉样蛋白相互作用进行了表征。TTR与不同的β-淀粉样蛋白肽种类结合：可溶性（解离常数，28 nM）、寡聚体和原纤维；不同的TTR变体与β-淀粉样蛋白的结合存在差异。透射电子显微镜（TEM）分析表明，TTR能够通过抑制和破坏纤维形成来干扰β-淀粉样蛋白纤维化。两种分子共同孵育导致β-淀粉样蛋白毒性消失。我们的结果证实TTR是一种β-淀粉样蛋白配体，并表明抑制/破坏β-淀粉样蛋白原纤维是TTR在AD中发挥保护作用的潜在机制。