Truncating tau reveals different pathophysiological actions of oligomers in single neurons.
Truncating tau reveals different pathophysiological actions of oligomers in single neurons.
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DOI：
10.1038/s42003-021-02791-x
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发表时间：
2021-11-04
影响因子：
5.9
通讯作者：
Wall MJ
中科院分区：
文献类型：
--
作者：
Hill E;Karikari TK;Lantero-Rodriguez J;Zetterberg H;Blennow K;Richardson MJ;Wall MJ
Tau蛋白参与维持神经元结构。在阿尔茨海默病中，少量的tau分子可以聚集形成寡聚体。然而，这些寡聚体如何产生神经元功能的变化仍不清楚。以前，发现由全长人tau制成的寡聚体对神经元特性具有多种影响。在这里，我们将tau分子切割成两部分：前123个氨基酸和剩余的124-441个氨基酸。这些截短的tau分子对神经元特性有特定的影响，使我们能够将全长tau的作用分配给分子的不同区域。我们确定了tau效应的一个关键靶点，电压门控钠通道，这可以解释tau对动作电位的影响。通过截短tau分子，我们已经探索了tau功能障碍的机制，并且这种对tau病理作用的理解将有助于开发未来的tau靶向疗法。Hill等人研究了全长或截短的人重组tau蛋白对小鼠海马锥体神经元兴奋性的影响。他们的结果表明，可以使用tau截短将全长tau寡聚体观察到的效应分开，并突出了电压门控钠通道电流中的tau介导的改变。
Tau protein is involved in maintaining neuronal structure. In Alzheimer’s disease, small numbers of tau molecules can aggregate to form oligomers. However, how these oligomers produce changes in neuronal function remains unclear. Previously, oligomers made from full-length human tau were found to have multiple effects on neuronal properties. Here we have cut the tau molecule into two parts: the first 123 amino acids and the remaining 124-441 amino acids. These truncated tau molecules had specific effects on neuronal properties, allowing us to assign the actions of full-length tau to different regions of the molecule. We identified one key target for the effects of tau, the voltage gated sodium channel, which could account for the effects of tau on the action potential. By truncating the tau molecule, we have probed the mechanisms that underlie tau dysfunction, and this increased understanding of tau’s pathological actions will build towards developing future tau-targeting therapies. Hill et al. examine the effects of full-length or truncated human recombinant tau on the excitability of hippocampal pyramidal neurons in mice. Their results suggest that effects seen with full-length tau oligomers can be dissected apart using tau truncations and highlights a tau-mediated alteration in voltage-gated sodium channel currents.
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DOI：
10.1007/s12031-011-9589-0
发表时间：
2011-11
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
Dickson DW;Kouri N;Murray ME;Josephs KA
通讯作者：
Josephs KA
影响因子：
2.9
作者：
Karikari TK;Nagel DA;Grainger A;Clarke-Bland C;Hill EJ;Moffat KG
通讯作者：
Moffat KG
影响因子：
16.2
作者：
Hoover, Brian R.;Reed, Miranda N.;Su, Jianjun;Penrod, Rachel D.;Kotilinek, Linda A.;Grant, Marianne K.;Pitstick, Rose;Carlson, George A.;Lanier, Lorene M.;Yuan, Li-Lian;Ashe, Karen H.;Liao, Dezhi
通讯作者：
Liao, Dezhi
影响因子：
12.7
作者：
Cicognola, Claudia;Brinkmalm, Gunnar;Hoglund, Kina
通讯作者：
Hoglund, Kina
影响因子：
3.9
作者：
Cowan, Catherine M.;Chee, Francis;Mudher, Amritpal
通讯作者：
Mudher, Amritpal