Department of Drug Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy.
Eur J Pharmacol. 2017 Dec 15;817:71-75. doi: 10.1016/j.ejphar.2017.05.057. Epub 2017 May 31.
Conceived more than 25 years ago, the amyloid cascade hypothesis of Alzheimer's disease has evolved to accommodate new findings, namely different forms of β-amyloid aggregates and downstream dysfunctions. Yet, the cascade does not mention its very beginning, the β-amyloid monomer. Here, I will discuss the monomer from a functional evolutionary perspective, highlighting the potential advantages of a native unfolded state that, however, involves an amyloidogenic risk. Finally, I will make a summary of what is known about its functional role in the brain and discuss the implications of its conceivable shortage in the development of Alzheimer's disease.
25 多年前提出的阿尔茨海默病淀粉样蛋白级联假说，随着新发现的不断出现，已经发展到能够容纳不同形式的β-淀粉样蛋白聚集物和下游功能障碍。然而，该级联假说并未提及它的起点，即β-淀粉样蛋白单体。在这里，我将从功能进化的角度来讨论单体，强调天然无规卷曲状态的潜在优势，但这也涉及到淀粉样蛋白形成的风险。最后，我将总结一下目前已知的其在大脑中的功能作用，并讨论其在阿尔茨海默病发展过程中可能缺乏的影响。
