Mixed Phospholipid Vesicles Catalytically Inhibit and Reverse Amyloid Fibril Formation.
Mixed Phospholipid Vesicles Catalytically Inhibit and Reverse Amyloid Fibril Formation.
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DOI：
10.1021/acs.jpclett.0c02074
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发表时间：
2020-09-03
影响因子：
5.7
通讯作者：
Kaar, Joel L.
中科院分区：
文献类型：
--
作者：
Chaparro Sosa, Andres F.;da Silva, Sabrina Matos de Oliveira;Morgan, Garry P.;Schwartz, Daniel K.;Kaar, Joel L.
虽然许多减少淀粉样蛋白-β（Aβ）原纤化的方法旨在减缓原纤维形成，但原纤维的降解仍然具有挑战性。我们提供了深入了解原纤维降解以及抑制纤维形成的脂质囊泡组成的1，2-二油酰基-sn-甘油-3-磷酸胆碱和1，2-二油酰基-sn-甘油-3-磷酸-（1 '-rac-甘油）。在囊泡与最佳脂质组合物的存在下，原纤维的形成被抑制高达76%。此外，通过调节脂质组成，成熟原纤维含量降低高达74%，Aβ的β-折叠含量显著降低。原纤维和β-折叠含量的减少与原纤维直径的减少一致，并且可以归因于混合囊泡的伴侣样活性。在证明这种显著活性的同时，我们的研究结果提供了新的证据，即脂质组成对脂质双层和Aβ肽/原纤维之间的相互作用强度具有显著影响。这种理解在治疗蛋白质错误折叠疾病方面具有有趣的治疗意义。
While many approaches to reduce fibrillation of amyloid-β (Aβ) have been aimed at slowing fibril formation, the degradation of fibrils remains challenging. We provide insight into fibril degradation as well as the inhibition of fiber formation by lipid vesicles composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol). In the presence of vesicles with the optimal lipid composition, fibril formation was inhibited up to 76%. Additionally, by tuning the lipid composition, mature fibril content decreased up to 74% and the β-sheet content of Aβ was significantly reduced. The reduction in fibril and β-sheet content was consistent with a decrease in fibril diameter and could be attributed to the chaperone-like activity of the mixed vesicles. While demonstrating this remarkable activity, our findings present new evidence that lipid composition has a significant effect on the strength of the interaction between lipid bilayers and Aβ peptides/fibrils. This understanding has intriguing therapeutic implications in treating protein misfolding diseases.
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