C-Terminally Truncated Forms of Tau, But Not Full-Length Tau or Its C-Terminal Fragments, Are Released from Neurons Independently of Cell Death
C-Terminally Truncated Forms of Tau, But Not Full-Length Tau or Its C-Terminal Fragments, Are Released from Neurons Independently of Cell Death
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DOI：
10.1523/jneurosci.0387-15.2015
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发表时间：
2015-07-29
影响因子：
5.3
通讯作者：
Walsh, Dominic M.
中科院分区：
文献类型：
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作者：
Kanmert, Daniel;Cantlon, Adam;Walsh, Dominic M.
最近的证据表明，tau聚集可能通过细胞外释放和随后的突触连接神经元的摄取而传播，但对tau释放的过程或细胞外tau的分子形式知之甚少。为了深入了解细胞外tau蛋白的性质，我们使用了高度灵敏的ELISA，当串联使用时，能够区分全长（FL）tau蛋白、中间区片段和C-末端（CT）片段。我们应用这些试验的N2 a细胞，诱导多能干细胞衍生的人皮层神经元，和原代大鼠皮层神经元，其中每一个仔细评估的生存能力的条件培养基的系统研究。在所有三种神经元模型中，细胞外tau蛋白的大部分是自由漂浮和未聚集的，
Recent evidence suggests that tau aggregation may spread via extracellular release and subsequent uptake by synaptically connected neurons, but little is known about the processes by which tau is released or the molecular forms of extracellular tau. To gain insight into the nature of extracellular tau, we used highly sensitive ELISAs, which, when used in tandem, are capable of differentiating between full-length (FL) tau, mid-region-bearing fragments, and C-terminal (CT) fragments. We applied these assays to the systematic study of the conditioned media of N2a cells, induced pluripotent stem cell-derived human cortical neurons, and primary rat cortical neurons, each of which was carefully assessed for viability. In all three neuronal models, the bulk of extracellular tau was free-floating and unaggregated and