BACKGROUND Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaque and neurofibrillary tangle formation, respectively. Neurofibrillary tangles form as a result of the intracellular accumulation of hyperphosphorylated tau. Telomerase activity and levels of the human reverse transcriptase (hTERT) subunit of telomerase are significantly decreased in AD. Recently, it has been demonstrated that the 37 kDa/67 kDa laminin receptor (LRP/LR) interacts with telomerase and is implicated in Aβ pathology. Since both LRP/LR and telomerase are known to play a role in the Aβ facet of AD, we hypothesized that they might also play a role in tauopathy. OBJECTIVE This study aimed to determine if LRP/LR has a relationship with tau and whether overexpression of LRP::FLAG has an effect on tauopathy-related proteins. METHODS We employed confocal microscopy and FRET to determine whether LRP/LR and tau co-localize and interact. LRP::FLAG overexpression in HEK-293 and SH-SY5Y cells as well as analysis of tauopathy-related proteins was assessed by western blotting. RESULTS We demonstrate that LRP/LR co-localizes with tau in the perinuclear cell compartment and confirmed a direct interaction between LRP/LR and tau in HEK-293 cells. Overexpression of LRP::FLAG in HEK-293 and SH-SY5Y cells decreased total and phosphorylated tau levels with a concomitant decrease in PrPc levels, a tauopathy-related protein. LRP::FLAG overexpression also resulted in increased hTERT levels. CONCLUSION This data suggest that LRP/LR extends its role in AD through a direct interaction with tau, and recommend LRP::FLAG as a possible alternative AD therapeutic via decreasing phosphorylated tau levels.

中文翻译：

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LRP :: FLAG降低阿尔茨海默氏病细胞培养模型中的磷酸化Tau水平。

背景技术阿尔茨海默氏病（AD）的特征在于分别具有淀粉样蛋白-β（Aβ）斑块和神经原纤维缠结。神经原纤维缠结是由于磷酸化tau的细胞内积累而形成的。在AD中，端粒酶活性和端粒酶人类逆转录酶（hTERT）亚基的水平显着降低。最近，已经证明37kDa / 67kDa层粘连蛋白受体（LRP / LR）与端粒酶相互作用并且与Aβ病理学有关。由于已知LRP / LR和端粒酶均在AD的Aβ方面起作用，因此我们假设它们也可能在tauopathy中起作用。目的本研究旨在确定LRP / LR是否与tau有关，以及LRP :: FLAG的过表达是否对tauopathy相关蛋白产生影响。方法我们使用共聚焦显微镜和FRET来确定LRP / LR和tau是否共定位和相互作用。通过蛋白质印迹法评估了HEK-293和SH-SY5Y细胞中LRP :: FLAG的过表达以及与tauopathy相关的蛋白质的分析。结果我们证明LRP / LR与tau在核周细胞区室中共定位，并证实LRP / LR与tau在HEK-293细胞中具有直接相互作用。LRP :: FLAG在HEK-293和SH-SY5Y细胞中的过表达降低了总tau和磷酸化的tau水平，同时降低了与tau蛋白相关的蛋白PrPc水平。LRP :: FLAG过表达也导致hTERT水平升高。结论这些数据表明LRP / LR通过与tau的直接相互作用扩展了其在AD中的作用，并建议使用LRP：