FK506 binding protein 12 differentially accelerates fibril formation of wild type alpha-synuclein and its clinical mutants A30P or A53T
FK506 binding protein 12 differentially accelerates fibril formation of wild type alpha-synuclein and its clinical mutants A30P or A53T
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DOI：
10.1111/j.1471-4159.2008.05342.x
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发表时间：
2008-07-01
影响因子：
4.7
通讯作者：
Engelborghs, Yves
中科院分区：
文献类型：
--
作者：
Gerard, Melanie;Debyser, Zeger;Engelborghs, Yves
α-突触核蛋白聚集(α-SYN)在帕金森病中起着关键作用。我们先前已经证明，添加FK506结合蛋白(FKBP)可以加速α-SYN的体外聚集，并且这种作用可以被这些酶的特异性抑制剂FK506所抵消。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对这两个临床突变体α-SYN的纤维形成的影响要小得多。使用失活的酶，我们能够区分对这两个过程有不同影响的催化和非催化效应。提出了一个解释非线性浓度依赖关系的模型。
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.