Alpha-synuclein is a lipid-binding protein expressed in neurons and oligodendrocytes which is increased in Parkinson's disease. We identified two putative liver X receptor (LXR) response elements in the human alpha-synuclein gene and used synthetic (TO901317, GW3695) and physiological (27-hydroxycholesterol) LXR activators to assess regulation of alpha-synuclein. LXR ligands upregulated alpha-synuclein mRNA by two-five-fold in human SK-N-SH neurons and three-six-fold in human MO3.13 oligodendrocytes. Significant 50% to four-fold induction of alpha-synuclein protein was also detected. Under these conditions, mRNA for LXR-responsive gene ABCA1 was significantly upregulated 15-40-fold and 5-25-fold in neurons and oligodendrocytes, respectively. LXR may, therefore, contribute to the regulation of alpha-synuclein expression in neurons and oligodendrocytes.

译文

α-突触核蛋白是一种在神经元和少突胶质细胞中表达的脂质结合蛋白,在帕金森氏病中会增加。我们在人类 α-突触核蛋白基因中鉴定了两个假定的肝X受体 (LXR) 反应元件,并使用合成 (TO901317,GW3695) 和生理 (27-羟基胆固醇) LXR激活剂来评估 α-突触核蛋白的调节。LXR配体将 α-突触核蛋白mRNA在人sk-n-sh神经元中上调了2-5倍,在人MO3.13少突胶质细胞中上调了3-6倍。还检测到对四倍 α-突触核蛋白诱导的显著50%。在这些条件下,LXR响应基因ABCA1的mRNA在神经元和少突胶质细胞中分别显着上调15-40倍和5-25倍。因此,LXR可能有助于调节神经元和少突胶质细胞中 α-突触核蛋白的表达。

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