Davies Paul, Fontaine Sarah N, Moualla Dima, Wang Xiaoyan, Wright Josephine A, Brown David R
Department of Biology and Biochemistry, University of Bath, Bath, UK.
Biochem Soc Trans. 2008 Dec;36(Pt 6):1299-303. doi: 10.1042/BST0361299.
Neurodegenerative diseases remain perplexing and problematic for modern research. Those associated with amyloidogenic proteins have often been lumped together simply because those proteins aggregate. However, research has identified a more logical reason to group some of these diseases together. The associated proteins not only aggregate, but also bind copper. The APP (amyloid precursor protein) binds copper in an N-terminal region. Binding of copper has been suggested to influence generation of beta-amyloid from the protein. PrP (prion protein) binds copper, and this appears to be necessary for its normal function and might also reduce its probability of conversion into an infectious prion. alpha-Synuclein, a protein associated with Parkinson's disease, also binds copper, but, in this case, it potentially increases the rate at which the protein aggregates. The similarities between these proteins, in terms of metal binding, has allowed us to investigate them using similar approaches. In the present review, we discuss some of these approaches.
神经退行性疾病对于现代研究而言仍然是令人困惑且存在问题的。那些与淀粉样蛋白相关的疾病常常仅仅因为这些蛋白会聚集而被归为一类。然而，研究已经发现了一个更合理的将其中一些疾病归为一类的原因。相关蛋白不仅会聚集，还会结合铜。淀粉样前体蛋白（APP）在其N端区域结合铜。有人提出铜的结合会影响该蛋白生成β-淀粉样蛋白。朊病毒蛋白（PrP）结合铜，这似乎对其正常功能是必要的，并且可能还会降低其转化为感染性朊病毒的概率。α-突触核蛋白是一种与帕金森病相关的蛋白，它也结合铜，但在这种情况下，它可能会增加该蛋白聚集的速率。这些蛋白在金属结合方面的相似性使我们能够使用相似的方法对它们进行研究。在本综述中，我们将讨论其中一些方法。
