Reduced levels of brain gangliosides GD1a, GD1b, GT1b and to a lesser extent GM1 have been found in substantia nigra (SN) from Parkinson's disease (PD) patients, along with decreased gene expression for key enzymes (B3Galt4, St3gal2) involved in synthesis of these gangliosides. Based on these observations, the present study examined the extent to which decreased expression of B3GALT4 mRNA and resulting decreased levels of GM1 ganglioside in dopaminergic cells may increase the vulnerability of these cells to degeneration in response to a neurotoxicant exposure that under normal circumstances would not result in neurodegeneration. Differentiated SK-N-SH cells were treated with B3GALT4 siRNA to significantly reduce B3GALT4 mRNA expression and decrease GM1 levels. Exposure of these cells to a low concentration (10 μM) of the neurotoxin MPP⁺ that previously produced no toxicity resulted in approximately 50% cell loss after B3GALT4 siRNA treatment. This was a similar a degree of cell loss observed with 100 μM MPP⁺ in normal, differentiated SK-N-SH cells. Addition of GM1 to the culture medium after siRNA treatment was able to significantly protect cells from enhanced MPP⁺ toxicity. These data suggest that decreased B3GALT4 and GM1 expression can increase cell vulnerability to potentially toxic stressors and that such mechanisms may contribute to dopaminergic neurodegeneration in PD.

在帕金森氏病（PD）患者的黑质（SN）中发现脑神经节苷脂GD1a，GD1b，GT1b和GM1的含量降低，并且参与合成P450的关键酶（B3Galt4，St3gal2）的基因表达降低这些神经节苷脂。基于这些观察结果，本研究检查了多巴胺能细胞中B3GALT4 mRNA表达降低以及由此导致的GM1神经节苷脂水平降低的程度，可能会增加这些细胞在正常情况下不会引起神经毒性的情况下对变性的脆弱性。在神经变性中。用B3GALT4 siRNA处理分化的SK-N-SH细胞，以显着降低B3GALT4 mRNA表达并降低GM1水平。将这些细胞暴露于低浓度（10μM）的神经毒素MPP中⁺先前未产生毒性的B3GALT4 siRNA处理后导致大约50％的细胞丢失。这与在正常，分化的SK-N-SH细胞中用100μMMPP ⁺观察到的细胞损失程度相似。siRNA处理后，向培养基中添加GM1能够显着保护细胞免受MPP ⁺毒性的增强。这些数据表明，降低的B3GALT4和GM1表达可以增加细胞对潜在毒性应激源的脆弱性，并且这种机制可能有助于PD中的多巴胺能神经退行性变。