Department of Pharmacology, University of North Dakota, School of Medicine and Health Sciences, 504 Hamline Street, Neuroscience Building, Grand Forks, ND 58203, USA.
Neurochem Res. 2011 Jun;36(6):994-1004. doi: 10.1007/s11064-011-0439-9. Epub 2011 Mar 8.
Alpha (α)-synuclein neuronal effects are continually being defined although its role in regulating glial phenotypes remains unclear. An ability to regulate microglial activation was investigated using primary cultures from wild type and α-synuclein deficient mice (Snca-/-). Snca-/- microglia demonstrated increased secretion of the cytokine tumor necrosis factor-alpha (TNF-α), impaired phagocytic ability, elevated prostaglandin levels, and increased protein levels of key enzymes in lipid-mediated signaling events, cytosolic phospholipase (cPLA(2)), cyclooxygenase-2 (Cox-2) and phospholipase D2 (PLD2) when compared to wild type cells. Increased cytokine secretion and cPLA(2) and Cox-2 levels in Snca-/- microglia were partially attenuated by inhibiting PLD-dependent signaling with n-butanol treatment.
尽管α-突触核蛋白在调节神经胶质表型中的作用仍不清楚，但它对神经元的影响一直在被定义。本研究使用野生型和α-突触核蛋白缺陷型（Snca-/-）小鼠的原代培养物，研究了其调节小胶质细胞激活的能力。与野生型细胞相比，Snca-/-小胶质细胞表现出细胞因子肿瘤坏死因子-α（TNF-α）分泌增加、吞噬能力受损、前列腺素水平升高、以及脂质介导信号事件中的关键酶的蛋白水平升高，如胞质型磷脂酶（cPLA（2））、环氧化酶-2（Cox-2）和磷脂酶 D2（PLD2）。用正丁醇处理抑制 PLD 依赖性信号转导，可部分减弱 Snca-/-小胶质细胞中细胞因子分泌以及 cPLA（2）和 Cox-2 水平的增加。
