Radwan Mona, Wood Rebecca J, Sui Xiaojing, Hatters Danny M
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, 30 Flemington Road, Melbourne, Victoria, Australia.
IUBMB Life. 2017 Feb;69(2):49-54. doi: 10.1002/iub.1597. Epub 2017 Jan 9.
Protein aggregation is a hallmark of the major neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's and motor neuron and is a symptom of a breakdown in the management of proteome foldedness. Indeed, it is remarkable that under normal conditions cells can keep their proteome in a highly crowded and confined space without uncontrollable aggregation. Proteins pose a particular challenge relative to other classes of biomolecules because upon synthesis they must typically follow a complex folding pathway to reach their functional conformation (native state). Non-native conformations, including the unfolded nascent chain, are highly prone to aberrant interactions, leading to aggregation. Here we review recent advances in knowledge of proteostasis, approaches to monitor proteostasis and the impact that protein aggregation has on biology. We also include discussion of the outstanding challenges. © 2017 IUBMB Life, 69(2):49-54, 2017.
蛋白质聚集是包括阿尔茨海默病、帕金森病、亨廷顿病和运动神经元病在内的主要神经退行性疾病的一个标志，是蛋白质组折叠管理出现故障的一种症状。事实上，值得注意的是，在正常情况下，细胞能够将其蛋白质组保持在一个高度拥挤和受限的空间内，而不会发生无法控制的聚集。相对于其他种类的生物分子而言，蛋白质带来了一个特殊的挑战，因为在合成后它们通常必须遵循一条复杂的折叠途径才能达到其功能构象（天然状态）。非天然构象，包括未折叠的新生链，极易发生异常相互作用，从而导致聚集。在此，我们综述了蛋白质稳态知识、监测蛋白质稳态的方法以及蛋白质聚集对生物学的影响方面的最新进展。我们还讨论了悬而未决的挑战。© 2017国际生物化学与分子生物学联盟生命科学，69(2):49 - 54，2017年。
