Neuroprotective effects of urate are mediated by augmenting astrocytic glutathione synthesis and release.

摘要: Urate has emerged as a promising target for neuroprotection based on epidemiological observations, preclinical models, and early clinical trial results in multiple neurologic diseases, including Parkinson's disease (PD). This study investigates the astrocytic mechanism of urate's neuroprotective effect. Targeted biochemical screens conditioned medium from urate- versus vehicle-treated astrocytes identified markedly elevated glutathione (GSH) concentrations candidate mediator astrocyte-dependent effects. treatment also induced nuclear translocation factor (erythroid-derived 2)-like 2 (Nrf2) protein transcriptional activation its key genes primary cultures. Urate's effect was attenuated when GSH depleted media either by targeting synthesis or release astrocytes. Overall, these implicate extracellular mediating protective urate cellular model PD. These show that can employ novel indirect via induction Nrf2 signaling pathway, master regulator response to oxidative stress,