Analysis of neuroprotective actions using progranulin-deficient neurons

我们发现，缺乏前颗粒蛋白（PGRN）（一种多功能生长因子）的神经元容易受到谷氨酸的兴奋性毒性。在本研究中，我们建立了分析PGRN缺失小鼠和PGRN被siRNA降低的人SH-SY5Y细胞培养的神经细胞的神经保护作用的实验系统。通过这些检测系统，我们发现PGRN对两种细胞都有神经保护作用，但作用在神经祖细胞和成熟神经元之间有所不同，这表明PGRN在保护神经元免受兴奋性毒性方面发挥作用，尽管其作用可能取决于神经元细胞的分化阶段。

We have found that neurons deficient of progranulin(PGRN), a multifunctional growth factor, are vulnerable to excitotoxicity of glutamate. In the present study, we established the assay system for analyzing neuroprotective actions using cultured neuronal cells derived from PGRN-deficient mice as well as human SH-SY5Y cells whose PGRN was reduced by siRNA. By means of these assay systems, we found that PGRN exerted neuroprotective actions on both cells, but the actions differed between neural progenitor cells and mature neurons, suggesting that PGRN plays a role in protecting neurons from excitotoxicity regardless of species, though its actions may vary depending on the stages of differentiation of neuronal cells.