Seventy years ago, we learned from Chris Anfinsen that the stereochemical code necessary to fold a protein is embedded into its amino acid sequence. In water, protein morphogenesis is a spontaneous reversible process leading from an ensemble of disordered structures to the ordered functionally competent protein; conforming to Aristotle's definition of substance, the synolon of matter and form. The overall process of folding is generally consistent with a two state transition between the native and the denatured protein: not only the denatured state is an ensemble of several structures, but also the native protein populates distinct functionally relevant conformational (sub)states. This two-state view should be revised, given that any globular protein can populate a peculiar third state called amyloid, characterized by an overall architecture that at variance with the native state, is by-and-large independent of the primary structure. In a nut shell, we should accept that beside the folded and unfolded states, any protein can populate a third state called amyloid which gained center stage being the hallmark of incurable neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases as well as others. These fatal diseases are characterized by clear-cut clinical differences, yet display some commonalities such as the presence in the brain of amyloid deposits constituted by one misfolded protein specific for each disease. Some aspects of this complex problem are summarized here as an excursus from the prion's fibrils observed in the brain of aborigines who died of Kuru to the amyloid detectable in the cortex of Alzheimer's patients.

中文翻译：

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从库鲁到阿尔茨海默病：个人观点

七十年前，我们从 Chris Anfinsen 那里了解到折叠蛋白质所需的立体化学密码已嵌入其氨基酸序列中。在水中，蛋白质形态发生是一个自发的可逆过程，从无序结构的集合到有序的功能性蛋白质。符合亚里士多德对物质的定义，物质与形式的共生。折叠的整个过程通常与天然蛋白质和变性蛋白质之间的两种状态转换一致：不仅变性状态是几种结构的集合，而且天然蛋白质也具有不同的功能相关构象（亚）状态。鉴于任何球状蛋白都可以形成一种特殊的第三种状态，称为淀粉样蛋白，因此应该修改这种两种状态的观点，其特点是与原生状态不同的整体架构，大体上独立于主要结构。简而言之，我们应该接受除了折叠和展开状态之外，任何蛋白质都可以填充称为淀粉样蛋白的第三种状态，该状态成为无法治愈的神经退行性疾病的标志，例如阿尔茨海默病和帕金森病以及其他疾病。这些致命疾病的特点是明显的临床差异，但表现出一些共性，例如大脑中存在由每种疾病特有的错误折叠蛋白质构成的淀粉样蛋白沉积物。这个复杂问题的某些方面在这里总结为从死于库鲁的原住民大脑中观察到的朊病毒原纤维到阿尔茨海默氏症皮质中可检测到的淀粉样蛋白的一个分支。