Non-conjugated small molecule FRET for differentiating monomers from higher molecular weight amyloid beta species.
Non-conjugated small molecule FRET for differentiating monomers from higher molecular weight amyloid beta species.
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DOI：
10.1371/journal.pone.0019362
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发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Moore A
中科院分区：
文献类型：
--
作者：
Ran C;Zhao W;Moir RD;Moore A
淀粉样蛋白(Aβ)的系统分化对阿尔茨海默病(AD)的诊断具有重要意义。尽管取得了重大进展，但关于哪些物种是AD病理的主要贡献者，以及哪些物种可以作为诊断AD的最佳生物标志物，仍存在争议。这些争议的部分原因是缺乏可靠的方法来区分复杂的Aβ亚型。特别是，将Aβ单体与有毒的高分子量物种区分开来，将有利于药物筛选、诊断和分子机制研究。然而，针对这些特定目标的快速而廉价的方法仍然缺乏。我们证明了一种非共轭FRET(Förster共振能量转移)技术的可行性，该技术利用淀粉样β蛋白(Aβ)作为FRET对组装的内在平台。当两个结构相似的姜黄素衍生物作为小分子FRET对与Aβ40聚集体混合时，产生FRET信号，而使用Aβ40单体溶液时检测不到信号。最后，这种FRET技术使我们能够定量Aβ单体和高分子量物种在溶液中的浓度。我们认为，这种FRET技术有可能被用作筛选Aβ聚集抑制物的工具。我们还建议，这个概念可以推广到其他错误折叠的蛋白质/肽，包括糖尿病的淀粉样蛋白，牛海绵状脑病的Prion，AD的tau蛋白，以及帕金森病的α-突触核蛋白。
Systematic differentiation of amyloid (Aβ) species could be important for diagnosis of Alzheimer's disease (AD). In spite of significant progress, controversies remain regarding which species are the primary contributors to the AD pathology, and which species could be used as the best biomarkers for its diagnosis. These controversies are partially caused by the lack of reliable methods to differentiate the complicated subtypes of Aβ species. Particularly, differentiation of Aβ monomers from toxic higher molecular weight species (HrMW) would be beneficial for drug screening, diagnosis, and molecular mechanism studies. However, fast and cheap methods for these specific aims are still lacking. We demonstrated the feasibility of a non-conjugated FRET (Förster resonance energy transfer) technique that utilized amyloid beta (Aβ) species as intrinsic platforms for the FRET pair assembly. Mixing two structurally similar curcumin derivatives that served as the small molecule FRET pair with Aβ40 aggregates resulted in a FRET signal, while no signal was detected when using Aβ40 monomer solution. Lastly, this FRET technique enabled us to quantify the concentrations of Aβ monomers and high molecular weight species in solution. We believe that this FRET technique could potentially be used as a tool for screening for inhibitors of Aβ aggregation. We also suggest that this concept could be generalized to other misfolded proteins/peptides implicated in various pathologies including amyloid in diabetes, prion in bovine spongiform encephalopathy, tau protein in AD, and α-synuclein in Parkinson disease.
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影响因子：
3.7
作者：
Soscia SJ;Kirby JE;Washicosky KJ;Tucker SM;Ingelsson M;Hyman B;Burton MA;Goldstein LE;Duong S;Tanzi RE;Moir RD
通讯作者：
Moir RD
DOI：
10.1016/j.bbapap.2010.04.001
发表时间：
2010-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Biancalana M;Koide S
通讯作者：
Koide S
影响因子：
15
作者：
Ran, Chongzhao;Xu, Xiaoyin;Raymond, Scott B.;Ferrara, Brian J.;Neal, Krista;Bacskai, Brian J.;Medarova, Zdravka;Moore, Anna
通讯作者：
Moore, Anna
影响因子：
4.8
作者：
McLaurin, J;Golomb, R;Fraser, PE
通讯作者：
Fraser, PE
影响因子：
3.5
作者：
Venkateswarlu, S;Ramachandra, MS;Subbaraju, GV
通讯作者：
Subbaraju, GV