School of Medical and Molecular Biosciences (04.06.35A), University of Technology, Harris Street, Sydney, NSW 2007, Australia.
Exp Neurol. 2014 Mar;253:192-6. doi: 10.1016/j.expneurol.2013.12.010. Epub 2013 Dec 24.
Animals, in common with plants and microorganisms, synthesise proteins from a pool of 20 protein amino acids (plus selenocysteine and pyrolysine) (Hendrickson et al., 2004). This represents a small proportion (~2%) of the total number of amino acids known to exist in nature (Bell, 2003). Many 'non-protein' amino acids are synthesised by plants, and in some cases constitute part of their chemical armoury against pathogens, predators or other species competing for the same resources (Fowden et al., 1967). Microorganisms can also use selectively toxic amino acids to gain advantage over competing organisms (Nunn et al., 2010). Since non-protein amino acids (and imino acids) are present in legumes, fruits, seeds and nuts, they are ubiquitous in the diets of human populations around the world. Toxicity to humans is unlikely to have been the selective force for their evolution, but they have the clear potential to adversely affect human health. In this review we explore the links between exposure to non-protein amino acids and neurodegenerative disorders in humans. Environmental factors play a major role in these complex disorders which are predominantly sporadic (Coppede et al., 2006). The discovery of new genes associated with neurodegenerative diseases, many of which code for aggregation-prone proteins, continues at a spectacular pace but little progress is being made in identifying the environmental factors that impact on these disorders. We make the case that insidious entry of non-protein amino acids into the human food chain and their incorporation into protein might be contributing significantly to neurodegenerative damage.
动物与植物和微生物一样，从 20 种蛋白质氨基酸（加上硒代半胱氨酸和吡咯赖氨酸）的池合成蛋白质（Hendrickson 等人，2004 年）。这仅占自然界中已知存在的氨基酸总数的一小部分（~2%）（Bell，2003 年）。许多“非蛋白质”氨基酸是由植物合成的，在某些情况下，它们构成了植物化学防御机制的一部分，以抵御病原体、捕食者或其他争夺相同资源的物种（Fowden 等人，1967 年）。微生物也可以选择性地使用有毒氨基酸来获得相对于竞争生物的优势（Nunn 等人，2010 年）。由于非蛋白质氨基酸（和亚氨基酸）存在于豆类、水果、种子和坚果中，因此它们在世界各地人类饮食中无处不在。对人类的毒性不太可能是它们进化的选择因素，但它们显然有可能对人类健康造成不利影响。在这篇综述中，我们探讨了人类暴露于非蛋白质氨基酸与神经退行性疾病之间的联系。环境因素在这些主要为散发性的复杂疾病中起着重要作用（Coppede 等人，2006 年）。与神经退行性疾病相关的新基因的发现继续以惊人的速度进行，其中许多基因编码易于聚集的蛋白质，但在确定影响这些疾病的环境因素方面几乎没有取得进展。我们认为，非蛋白质氨基酸悄然进入人类食物链并被纳入蛋白质可能会对神经退行性损伤产生重大影响。
