Effect of metals on herbicides-α-synuclein association:: A possible factor in neurodegenerative disease studied by capillary electrophoresis
Effect of metals on herbicides-α-synuclein association:: A possible factor in neurodegenerative disease studied by capillary electrophoresis
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DOI：
10.1002/elps.200500169
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发表时间：
2005-09-01
期刊：
影响因子：
2.9
通讯作者：
Guillaume, YC
中科院分区：
文献类型：
--
作者：
André, C;Truong, TT;Guillaume, YC
α-突触核蛋白在黑质多巴胺能神经元的聚集是帕金森病（PD）的关键步骤。该病的病因尚不清楚，但最近的流行病学和实验研究重新引起了人们对环境因素，特别是除草剂和金属，在PD发病机制中发挥作用的假设的兴趣。首次用毛细管电泳法计算了α-突触核蛋白与5种除草剂的缔合常数。此外，一些金属对这种结合的效果进行了研究。似乎除草剂优先结合由锰、铝、镉、铜和锌诱导的α-突触核蛋白的部分折叠中间构象。然后，金属增加突触核蛋白-除草剂缔合。然而，该研究显示了与抗生素利福平和镁添加的对比作用，导致α-突触核蛋白-除草剂相互作用的降低，即使在本体溶剂中存在其他金属。考虑到流行病学研究，所有这些结果表明PD和相关身体疾病的潜在分子基础。
The aggregation of a-synuclein in the dopaminergic neurons of the substantia nigra is a critical step in the Parkinson's disease (PD). The etiology of the disease is unknown but recent epidemiological and experimental studies have renewed interest in the hypothesis that environmental factors, especially herbicides and metals, have a role on the pathogenesis of PD. For the first time, the association constants of a-synuclein with five herbicides have been calculated using a capillary electrophoresis (CE) method. In addition, the effect of a number of metals on this binding has been investigated. It appears that the herbicides preferentially bind to a partially folded intermediate conformation of a-synuclein induced by manganese, aluminium, cadmium, copper and zinc. Then, metal increases the synuclein-herbicide association. However, this study shows contrasting actions with the antibiotic rifampicin and magnesium addition leading to a decrease of the alpha-synuclein-herbicide interaction even if other metals are present in the bulk solvent. Considering epidemiological studies, all these results suggest an underlying molecular basis for PD and related body diseases.