Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons.
Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons.
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DOI：
10.1038/srep05715
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发表时间：
2014-07-17
影响因子：
4.6
通讯作者：
Leclerc N
中科院分区：
文献类型：
--
作者：
Mohamed NV;Plouffe V;Rémillard-Labrosse G;Planel E;Leclerc N
最近的研究表明，人类tau蛋白可以由神经元和非神经元细胞分泌，这是一个与大脑中tau蛋白病理学传播相关的事件。在本研究中，我们证实在生理条件下，在具有识别总tau的抗tau抗体和针对未磷酸化tau的Tau-1抗体的培养基中检测到一个tau阳性条带。然后，我们检查了tau分泌是否在损伤后被修饰。Tau分泌通过饥饿[Earle平衡盐溶液（EBSS）]、溶酶体功能抑制（亮抑酶肽）增加，并且当这两种条件叠加时，这种组合处理对Tau分泌具有最重要的影响。有趣的是，当神经元用单独的EBSS或EBSS +亮抑酶肽处理时，tau分泌的模式与对照神经元的tau分泌的模式不同。在这些条件下，在培养基中检测到三个tau阳性条带。这三条带中的两条对Tau-1抗体具有免疫反应性，表明在这些处理后释放了至少两种tau物质。总的来说，我们的结果表明，在神经退行性疾病中观察到的诸如营养剥夺和溶酶体功能障碍的损伤可能导致脑中tau分泌增加和tau病理学传播。
Recent studies have demonstrated that human tau can be secreted by neurons and non-neuronal cells, an event linked to the propagation of tau pathology in the brain. In the present study, we confirmed that under physiological conditions, one tau-positive band was detected in the culture medium with an anti-tau antibody recognizing total tau and the Tau-1 antibody directed against unphosphorylated tau. We then examined whether tau secretion was modified upon insults. Tau secretion was increased by starvation [Earle's Balanced Salt Solution (EBSS)], inhibition of lysosomal function (leupeptin) and when both of these conditions were superimposed, this combined treatment having the most important effects on tau secretion. Interestingly, the pattern of tau secretion was distinct from that of control neurons when neurons were treated either with EBSS alone or EBSS + leupeptin. In these conditions, three tau-positive bands were detected in the culture medium. Two of these three bands were immunoreactive to Tau-1 antibody revealing that at least two tau species were released upon these treatments. Collectively, our results indicate that insults such as nutrient deprivation and lysosomal dysfunction observed in neurodegenerative diseases could result in an increase of tau secretion and propagation of tau pathology in the brain.
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影响因子：
3.5
作者：
Gomez-Ramos, A.;Diaz-Hernandez, M.;Avila, J.
通讯作者：
Avila, J.
影响因子：
34.7
作者：
Frost, Bess;Diamond, Marc I.
通讯作者：
Diamond, Marc I.
神经元中的自噬诱导和自噬体清除：与阿尔茨海默氏病自噬病理学的关系。
影响因子：
5.3
作者：
Boland, Barry;Kumar, Asok;Lee, Sooyeon;Platt, Frances M.;Wegiel, Jerzy;Yu, W. Haung;Nixon, Ralph A.
通讯作者：
Nixon, Ralph A.
影响因子：
5.3
作者：
Burkhart, KK;Beard, DC;Billingsley, ML
通讯作者：
Billingsley, ML
影响因子：
4.8
作者：
Karch, Celeste M.;Jeng, Amanda T.;Goate, Alison M.
通讯作者：
Goate, Alison M.