Neurotoxic protein oligomers - what you see is not always what you get
Neurotoxic protein oligomers - what you see is not always what you get
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DOI：
10.1080/13506120500106958
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发表时间：
2005-06-01
影响因子：
5.5
通讯作者：
Teplow, DB
中科院分区：
文献类型：
--
作者：
Bitan, G;Fradinger, EA;Teplow, DB
越来越多的证据表明，淀粉样蛋白的可溶性组装体是许多淀粉样蛋白相关疾病中的主要神经毒性物质。因此，淀粉样变性病理机制的研究重点已从淀粉样原纤维转向寡聚体。由于低聚物的亚稳态性质，其生物物理表征很困难。检测低聚物最流行的实验方法是 SDS-PAGE。然而，我们提供的实验证据表明 SDS-PAGE 并不是表征淀粉样蛋白寡聚体的可靠方法，并讨论了替代方法。此外，我们还讨论了不一致的命名法如何混淆了我们对蛋白质组装过程和产品的理解。本文的目的是确定与研究蛋白质寡聚物的方法和语言相关的陷阱并提供替代方案，从而促进成功阐明控制淀粉样蛋白寡聚物组装和毒性的机制。
An increasing body of evidence suggests that soluble assemblies of amyloid proteins are the predominant neurotoxic species in many amyloid-related diseases. Consequently, the focus of research on pathologic mechanisms underlying amyloidoses has shifted from amyloid fibrils to oligomers. Biophysical characterization of oligomers is difficult due to their metastable nature. The most popular experimental method for detection of oligomers has been SDS-PAGE. However, we provide experimental evidence that SDS-PAGE is not a reliable method for characterization of amyloid protein oligomers and discuss alternative approaches. In addition, we discuss how inconsistent nomenclature has obfuscated our understanding of the process and products of protein assembly. The goals of this paper are to identify pitfalls associated with the methods and language used to study protein oligomers and to provide alternatives, thereby facilitating successful elucidation of the mechanisms controlling amyloid protein oligomer assembly and toxicity.