Analysis of brain infiltrating monocyteic cell in lysosomal disease

GM2神经节苷脂病是一种溶酶体β -己糖氨酸酶（Hex）缺乏症，涉及未降解底物（包括GM2神经节苷脂（GM2））的过度积累和进行性神经退行性变。在本研究中，我们从Sandhoff病模型小鼠骨髓中分离单核细胞系，并证实单核细胞系的信号转导异常。我们发现SD单核细胞（MSD）的mip -1 α的细胞迁移与野生型（WT）小鼠分离的细胞相比有显著差异，MSD被激活。此外，我们观察到在MSD细胞中Cofilin磷酸化增加。此外，与WT相比，MSD中PI3K的活性增加了约5倍。这些结果表明MSD中PI3K的上调依赖于天然底物的积累，包括GM2。这些发现可能代表了在GM2神经节脂质病中观察到的将浸润细胞连接到大脑的机制。

GM2 gangliosidosis is a lysosomal beta-hexosaminidase (Hex) deficiency involving excessive accumulation of undegraded substrates, including GM2 ganglioside (GM2), and progressive neurodegeneration. In this study, we isolated monocyte cell line from the bone marrow of Sandhoff disease model mice, and demonstrated the abnormalities of signal transduction in monocyte cell lines. We found remarkable differences in the cell migraion for MIP-1alpha of SD monocyte (MSD) when compared to cells isolated from wild type (WT) mice, with activation of MSD. In addition, we observed increased Cofilin phosphorylation in MSD cells. Moreover, PI3K activity was increased about 5times in MSD compare with that of WT. These results suggest that the up-regulation of PI3K of MSD was dependent upon accumulation of natural substrates, including GM2. These findings may represent a mechanism in linking infiltrating cells into brain observed in GM2 gangliosidosis.