Gerard Melanie, Debyser Zeger, Desender Linda, Baert Johan, Brandt Inger, Baekelandt Veerle, Engelborghs Yves
Laboratory of Biomolecular Dynamics, K. U. Leuven, Flanders, Belgium.
J Neurochem. 2008 Jul;106(1):121-33. doi: 10.1111/j.1471-4159.2008.05342.x. Epub 2008 Jul 1.
Aggregation of alpha-synuclein (alpha-SYN) plays a key role in Parkinson's disease. We have previously shown that aggregation of alpha-SYN in vitro is accelerated by addition of FK506 binding proteins (FKBP) and that this effect can be counteracted by FK506, a specific inhibitor of these enzymes. In this paper, we investigated in detail the effect of FKBP12 on early aggregation and on fibril formation of wild-type, A53T and A30P alpha-SYN. FKBP12 has a much smaller effect on the fibril formation of these two clinical mutants alpha-SYN. Using an inactive enzyme, we were able to discriminate between catalytic and non-catalytic effects that differentially influence the two processes. A model explaining non-linear concentration dependencies is proposed.
α-突触核蛋白（α-SYN）的聚集在帕金森病中起关键作用。我们之前已经表明，在体外添加FK506结合蛋白（FKBP）可加速α-SYN的聚集，并且这种作用可被这些酶的特异性抑制剂FK506抵消。在本文中，我们详细研究了FKBP12对野生型、A53T和A30Pα-SYN早期聚集和纤维形成的影响。FKBP12对这两种临床突变型α-SYN的纤维形成影响要小得多。使用一种无活性的酶，我们能够区分对这两个过程有不同影响的催化和非催化作用。提出了一个解释非线性浓度依赖性的模型。
