Amyloid formation: functional friend or fearful foe?
Amyloid formation: functional friend or fearful foe?
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DOI：
10.1111/joim.12479
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发表时间：
2016-08
影响因子：
11.1
通讯作者：
Münch J
中科院分区：
文献类型：
--
作者：
Bergman P;Roan NR;Römling U;Bevins CL;Münch J
淀粉样蛋白的形成在神经退行性疾病如阿尔茨海默病和帕金森病以及淀粉样变性的背景下研究得最多。然而，越来越清楚的是，淀粉样蛋白也存在于健康环境中;例如，无毒的淀粉样蛋白形成对于黑色素合成和先天免疫很重要。此外，细菌具有产生功能性淀粉样蛋白结构的机制，其在细菌生理学和与宿主细胞的相互作用中具有重要作用。在这里，我们将讨论人类和细菌中纤维形成蛋白的一些新方面。首先，将考虑抗微生物肽人防御素6（HD 6）的淀粉样蛋白形成特性。有趣的是，与其他抗菌肽不同，HD 6不会杀死细菌。然而，最近的数据表明，HD 6可以在肠道粘膜形成淀粉样结构，对细菌表面具有很强的亲和力。这些所谓的“纳米网”通过将细菌缠绕在网状结构中来阻止细菌入侵。接下来，将讨论人类精液中功能性淀粉样纤维的作用。这些纤维是通过它们增强HIV感染的特性而被发现的，但它们也可能具有其他未知的功能。最后，淀粉样蛋白的形成在细菌中的作用将进行审查。最近发现细菌可以以受控的方式制造淀粉样蛋白而没有毒性作用，这一发现特别令人感兴趣，可能对人类疾病有影响。淀粉样蛋白在健康和疾病中的作用开始被揭开，在这里我们将回顾这个令人兴奋的领域的一些最新发现。
Amyloid formation has been most studied in the context of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, as well as in amyloidosis. However, it is becoming increasingly clear that amyloid is also present in the healthy setting; for example non-toxic amyloid formation is important for melanin synthesis and in innate immunity. Furthermore, bacteria have mechanisms to produce functional amyloid structures with important roles in bacterial physiology and interaction with host cells. Here we will discuss some novel aspects of fibril-forming proteins in humans and bacteria. First, the amyloid-forming properties of the antimicrobial peptide human defensin 6 (HD6) will be considered. Intriguingly, unlike other antimicrobial peptides, HD6 does not kill bacteria. However, recent data show that HD6 can form amyloid structures at the gut mucosa with strong affinity for bacterial surfaces. These so-called ‘nanonets’ block bacterial invasion by entangling the bacteria in net-like structures. Next, the role of functional amyloid fibrils in human semen will be discussed. These fibrils were discovered through their property to enhance HIV infection but they may also have other yet unknown functions. Finally, the role of amyloid formation in bacteria will be reviewed. The recent finding that bacteria can make amyloid in a controlled fashion without toxic effects is of particular interest and may have implications for human disease. The role of amyloid in health and disease is beginning to be unraveled, and here we will review some of the most recent findings in this exciting area.