Microglia are the brain mononuclear phagocytes which plays a key role in neurodegenerative diseases, like Alzheimer's. Till date, microglia have been explored mostly for their neuro-inflammatory functions. Recent studies have shifted their focus towards less explored functions which involve non-autonomous clearance of protein aggregates. However, these functions are significantly affected by aging and neurodegeneration. In Alzheimer's disease (AD), microglia have been reported to clear amyloid beta (Aβ) deposits via phagocytosis or release various pro-inflammatory cytokines. Whether microglia could be beneficial or detrimental to the brain, it all depends upon the type and strength of stimulus. So, if their beneficial properties could be selectively harnessed without activating pro-inflammatory response, a potential therapeutic strategy could be developed to check the formation of protein aggregates like Aβ. In the present study, we have checked the effect of toxic amyloid beta oligomers (Aβo) on the microglial phagocytic activity. Our findings revealed that at lower concentrations, Aβo are not toxic to the cells and they can survive even with longer exposures but with decreased phagocytic activity. However, at higher concentrations Aβo become toxic and resulted in modulation of various genes which regulates microglial phagocytic activity. Sulforaphane (SFN) treatment has shown to induce the phagocytic activity of Aβo treated microglial cells. In addition, low dose Aβo and SFN treatment have not shown modulation in the levels of pro-inflammatory mediators of microglia. Taken together, these findings suggest that SFN treatment may ameliorate the Aβo mediated decrease in microglial phagocytic activity.

中文翻译：

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萝卜硫素可减弱介导的Aβ低聚物对小胶质细胞吞噬活性的降低。

小胶质细胞是大脑单核吞噬细胞，在像阿兹海默氏症这样的神经退行性疾病中起关键作用。迄今为止，小胶质细胞已被广泛研究其神经炎症功能。最近的研究已将其重点转移到较少探索的功能上，这些功能涉及非自主清除蛋白质聚集体。但是，这些功能会受到衰老和神经变性的严重影响。在阿尔茨海默氏病（AD）中，据报道小胶质细胞通过吞噬作用清除了淀粉样β（Aβ）沉积或释放了各种促炎性细胞因子。小胶质细胞对大脑有益还是有害，都取决于刺激的类型和强度。因此，如果可以在不激活促炎反应的情况下有选择地利用其有益特性，可以开发一种潜在的治疗策略来检查蛋白质聚集体（如Aβ）的形成。在本研究中，我们检查了毒性淀粉样β低聚物（Aβo）对小胶质细胞吞噬活性的影响。我们的发现表明，在较低的浓度下，Aβo对细胞无毒，即使暴露时间更长，但吞噬活性降低，它们仍可以存活。然而，在更高的浓度下，Aβo变得有毒，并导致调节小胶质细胞吞噬活性的各种基因的调节。萝卜硫素（SFN）处理已显示出可诱导Aβo处理的小胶质细胞的吞噬活性。此外，小剂量Aβo和SFN治疗尚未显示出对小胶质细胞促炎性介质水平的调节。在一起