Hirai Chihoko, Badawy Shaymaa Mohamed Mohamed, Zhang Lifang, Okada Taro, Kajimoto Taketoshi, Nakamura Shunichi
Division of Biochemistry, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Kobe J Med Sci. 2017 May 9;62(6):E162-E167.
α-Synuclein (α-Syn) is implicated in several neurodegenerative disorders, including Parkinson's disease, known collectively as the synucleinopathies. α-Syn is known to be secreted from the cells and may contribute to the progression of the disease. Although extracellular α-Syn is shown to impair platelet-derived growth factor-induced chemotaxis, molecular mechanism of α-Syn-induced motility failure remains elusive. Here we have aimed at phospholipase D (PLD) as a potential target for α-Syn and examined the involvement of this enzyme in α-Syn action. Indeed, extracellular α-Syn caused inhibition of agonist-induced PLD activation. However, inhibition of hydrolytic activity of PLD by 1-butanol treatment showed little or no effect on agonist-induced chemotaxis. These results suggest that some signaling pathways other than PLD may be involved in α-Syn-induced inhibition of chemotaxis.
α-突触核蛋白（α-Syn）与多种神经退行性疾病有关，包括统称为突触核蛋白病的帕金森病。已知α-Syn可从细胞中分泌出来，并可能促进疾病的进展。尽管细胞外α-Syn显示出会损害血小板衍生生长因子诱导的趋化作用，但α-Syn诱导运动功能障碍的分子机制仍不清楚。在这里，我们将磷脂酶D（PLD）作为α-Syn的潜在靶点，并研究了该酶在α-Syn作用中的参与情况。事实上，细胞外α-Syn导致激动剂诱导的PLD激活受到抑制。然而，用1-丁醇处理抑制PLD的水解活性对激动剂诱导的趋化作用几乎没有影响。这些结果表明，除PLD外的一些信号通路可能参与了α-Syn诱导的趋化作用抑制。
