Extracellular signal-regulated kinase is involved in alpha-synuclein-induced mitochondrial dynamic disorders by regulating dynamin-like protein 1
Extracellular signal-regulated kinase is involved in alpha-synuclein-induced mitochondrial dynamic disorders by regulating dynamin-like protein 1
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DOI：
10.1016/j.neurobiolaging.2012.02.001
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发表时间：
2012-12-01
影响因子：
4.2
通讯作者：
Chen, Sheng-Di
中科院分区：
文献类型：
--
作者：
Gui, Ya-Xing;Wang, Xin-Yi;Chen, Sheng-Di
复合证据表明，α-突触核蛋白（SNCA）通过诱导神经毒性在帕金森病（PD）的发病机制中起着重要作用。线粒体是高度动态的细胞器，经历融合和分裂过程，其失衡已被视为PD的关键触发因素。然而，SNCA和线粒体动力学之间的潜在关系仍不清楚。这项研究表明，SNCA过表达不仅改变了线粒体形态，但也显着增加线粒体分裂蛋白动力蛋白样蛋白1（DLP 1）的易位。为了进一步研究SNCA对线粒体动力学的影响机制，使用了蛋白质组学技术，细胞培养物中氨基酸的稳定同位素标记（SILAC）。细胞外信号调节激酶（ERK）被证实参与调节DLP 1和SNCA介导的神经毒性。最后，额外的结果表明，SNCA诱导的线粒体动力学紊乱和神经毒性可以通过姜黄素通过ERK抑制而得到改善，这意味着该试剂将来可以用于预防和治疗PD。(C)2012 Elsevier Inc. All rights reserved.
Compounding evidence suggests that alpha-synuclein (SNCA) plays an important role in the pathogenesis of Parkinson's disease (PD) by inducing neurotoxicity. Mitochondria are highly dynamic organelles that undergo fusion and fission processes, the imbalance of which has been viewed as a key trigger for PD. However, the underlying relationship between SNCA and mitochondrial dynamics remains unclear. This study demonstrated that SNCA overexpression not only altered mitochondrial morphology, but also significantly increased the translocation of mitochondrial fission protein dynamin-like protein 1 (DLP1). To further investigate the mechanism of SNCA's effect on mitochondrial dynamics, the proteomic technique, stable isotope labeling of amino acid in cell cultures (SILAC), was used. The extracellular signal-regulated kinase (ERK) was confirmed to be involved in the regulation of DLP1 and SNCA-mediated neurotoxicity. Finally, additional results demonstrated that SNCA inducing both mitochondrial dynamic disorders and neurotoxicity could be ameliorated by curcumin through ERK inhibition, which implied that the agent could be used to prevent and treat PD in the future. (C) 2012 Elsevier Inc. All rights reserved.