Alterations to the global levels of certain types of post-translational modifications (PTMs) are commonly observed in neurodegenerative diseases. The net influence of these PTM changes to the progression of these diseases can be deduced from cellular and animal studies. However, at the molecular level, how one PTM influences a given protein is not uniform and cannot be easily generalized from systemic observations, thus requiring protein-specific interrogations. Given that protein aggregation is a shared pathological hallmark in neurodegeneration, it is important to understand how these PTMs affect the behavior of amyloid-forming proteins. For this purpose, protein semisynthesis techniques, largely via native chemical and expressed protein ligation, have been widely used. These approaches have thus far led to our increased understanding of the site-specific consequences of certain PTMs to amyloidogenic proteins' endogenous function, their propensity for aggregation, and the structural variations these PTMs induce toward the aggregates formed.

中文翻译：

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蛋白质半合成揭示的淀粉样蛋白翻译后修饰的后果。

在神经退行性疾病中通常观察到某些类型的翻译后修饰 (PTM) 的全局水平的改变。这些 PTM 变化对这些疾病进展的净影响可以从细胞和动物研究中推断出来。然而，在分子水平上，一个 PTM 如何影响给定蛋白质并不一致，并且不能从系统观察中轻易概括，因此需要蛋白质特异性询问。鉴于蛋白质聚集是神经退行性变的共同病理标志，了解这些 PTM 如何影响淀粉样蛋白形成蛋白的行为非常重要。为此，主要通过天然化学和表达蛋白质连接的蛋白质半合成技术已被广泛使用。