Reductions in PP2A methylation were associated with a concomitant increase in each brain region of p-Tau at the PHF-1 epitope (Fig. 6A,B).
Incubation of human SH-SY5Y neuroblastoma cells for 2 h with L-dopa induced a dose-dependent decrease in both soluble and insoluble methylated PP2A C subunit levels, and concomitant accumulation of demethylated PP2A enzymes
Significantly, we found similar effects in human dopaminergic neurons (Fig. 2F). Treatment of neurons with L-Dopa induced a 40–49% decrease in methylated PP2A and concomitant 168–179% increase in endogenous p-Tau (PHF-1) levels (Fig. 2G).
Folate starvation in the presence of L-dopa resulted in a 200–210% increase in demethylated PP2A levels, and 235–250% increase in p-Tau levels in the dopaminergic neurons, relative to untreated controls maintained in NF medium.
Here, we found that administration of L-dopa led to a significant 5-fold increase in plasma tHcy concentrations, when compared to saline treated mice (Table 1). This L-dopa induced increase in plasma tHcy was significantly greater in mice that had been reared on either low folate (LF) or FD diets (Table 1).
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.