神经损伤与修复
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Figure 1｜Schematic illustration of impaired lipid homeostasis in SPG3A.
How do mutations of ATL1 in astrocytes result in cholesterol defects in cortical PNs? Our study revealed that ATL1 mutations dysregulated proteolipid gene expression including reduced expression of PLIN2, PLIN3, NR1H2 and apolipoprotein E (APOE). APOE is a critical mediator for cholesterol trafficking from glial cells to neurons. The APOE content in the medium was examined using ApoE enzyme-linked immunosorbent assay kit, and a significant reduction of APOE content in SPG3A culture medium was observed. Using cholesterol efflux analysis, we further found that the efflux of cholesterol from SPG3A astrocytes was specifically and significantly reduced compared with control astrocytes (Figure 1).