What amyloid ligands can tell us about molecular polymorphism and disease.
What amyloid ligands can tell us about molecular polymorphism and disease.
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DOI：
10.1016/j.neurobiolaging.2016.03.019
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发表时间：
2016-06
影响因子：
4.2
通讯作者：
Walker LC
中科院分区：
文献类型：
--
作者：
LeVine H 3rd;Walker LC
对活体受试者中淀粉样病变具有选择性的可穿透血脑屏障的正电子发射断层成像（PET）配体，在阿尔茨海默病进展的症状前生物标志物方面引发了一场革命。随着对其他化学结构的研究，配体结合位点的异质性变得明显，一些配体在人类疾病和动物模型之间的结合差异也是如此。这些差异及其影响很少受到关注。本综述讨论了不同配体结合位点和错误折叠的蛋白质构象多态性对不同配体所获取的成像数据解读的影响。对动物模型中结合差异的研究可能会确定病理过程，从而为改进这些模型提供信息，以便更真实地重现这种人类特有的疾病。特定配体对不同构象状态结合的差异选择性有可能被利用来更好地定义疾病进展并改进对临床结果的预测。
Brain-penetrant PET imaging ligands selective for amyloid pathology in living subjects have sparked a revolution in presymptomatic biomarkers for Alzheimer’s disease progression. As additional chemical structures were investigated, the heterogeneity of ligand binding sites became apparent, as did discrepancies in binding of some ligands between human disease and animal models. These differences and their implications have received little attention. This review discusses the impact of different ligand binding sites and misfolded protein conformational polymorphism on the interpretation of imaging data acquired with different ligands. Investigation of the differences in binding in animal models may identify pathological processes informing improvements to these models for more faithful recapitulation of this uniquely human disease. The differential selectivity for binding of particular ligands to different conformational states could potentially be harnessed to better define disease progression and improve the prediction of clinical outcomes.