Fig. 4: A glycosylation defect in GCase leads to significant retention in the Golgi apparatus, which subsequently results in LPC-induced abnormal accumulation of GlcCer. | npj Parkinson's Disease

Fig. 4: A glycosylation defect in GCase leads to significant retention in the Golgi apparatus, which subsequently results in LPC-induced abnormal accumulation of GlcCer.

From: Lysophosphatidylcholine promoting α-Synuclein aggregation in Parkinson’s disease: disrupting GCase glycosylation and lysosomal α-Synuclein degradation

Fig. 4

a, b Western blot experiments assessing the expression level of non-glycosylated GCase in MES23.5 dopaminergic neurons after treatment with glycosidic endonuclease Endo-H (n = 3, Control vs Endo-H, t = 7.996, p = 0.0013). c, d Western blot analyses of non-glycosylated GCase expression in MES23.5 dopaminergic neurons following intervention with different doses of LPC (n = 3, Control vs LPC5: p = 0.4962, ns, Control vs LPC10: p < 0.0001, Control vs LPC15: p = 0.0004). e, f Glycosylated/non-glycosylated GCase ratio in MES23.5 dopaminergic neurons analyzed via Western blotting after LPC treatment, CBE intervention, and ML198 administration (n = 3, Control vs LPC: p < 0.0001, Control vs CBE: p < 0.0001, LPC vs LPC + ML198: p = 0.0030). g Immunofluorescence co-labeling images of GCase and GM130 in MES23.5 dopaminergic neurons post-LPC intervention. h–j Statistical analysis of changes in the co-labeling degree of GCase and GM130 (n = 3, t = 4.331, p = 0.0123). k Immunofluorescence co-labeling image of GCase with LAMP1 in MES23.5 dopaminergic neurons after LPC intervention. l–n Statistical analysis of changes in the co-labeling degree of GCase and LAMP1 (n = 3, t = 11.30, p = 0.0003). O Heatmap illustrating alterations in the abundance of the glucosylceramide family in MES23.5 dopaminergic neurons following LPC intervention analyzed by high-performance liquid chromatography-mass spectrometry. p–s Western blot analyses were conducted to assess α-Synuclein expression in MES23.5 dopaminergic neurons following modulation of glucosylceramide levels. (n = 3, oligomers: Control vs LPC: p = 0.0004, Control vs CBE: p = 0.00002, Control vs ML198 + LPC: p = 0.0033; monomer: Control vs LPC: p = 0.0002, Control vs CBE: p < 0.00001, Control vs ML198 + LPC: p = 0.0023; oligomers/ monomer: Control vs LPC: p = 0.0052, Control vs CBE: p = 0.0007, LPC vs ML198 + LPC: p = 0.0428).

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