Different tau species lead to heterogeneous tau pathology propagation and misfolding.
Different tau species lead to heterogeneous tau pathology propagation and misfolding.
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DOI：
10.1186/s40478-018-0637-7
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发表时间：
2018-11-29
影响因子：
7.1
通讯作者：
Buée L
中科院分区：
文献类型：
--
作者：
Dujardin S;Bégard S;Caillierez R;Lachaud C;Carrier S;Lieger S;Gonzalez JA;Deramecourt V;Déglon N;Maurage CA;Frosch MP;Hyman BT;Colin M;Buée L
tau蛋白病是以神经元内的tau聚集为特征的异质性病理组。它们中的大多数是散发性的，但某些tau蛋白病依赖于tau基因（MAPT）突变。它们尤其因其不同的神经病理学特征而彼此不同，例如病变形状、受影响的区域和聚集体的分子组成。存在六种tau亚型，但它们并不都在每种tau病变中共聚集，而是每种都有独特的特征。在一些tau蛋白病如阿尔茨海默病（AD）中，tau蛋白聚集遵循刻板的解剖学阶段。最近的数据表明，这种进展是由于tau蛋白从神经元到神经元的传播的活跃过程。我们想知道tau亚型或突变如何影响tau聚集和tau传播的过程。在人类神经病理学材料中，我们发现与散发性AD患者中发现的tau相比，MAPT突变诱导更快的错误折叠。在大鼠脑中，我们观察到非病理性tau种类的细胞间转移，而不管测试的同种型或突变的存在。相比之下，我们发现tau的种类影响tau病理标志物的传播，例如过度磷酸化和错误折叠。事实上，当tau突变或同种型组成被修饰时，错误折叠和过度磷酸化的tau蛋白不会以相同的速率扩散。这些结果清楚地证明了tau的特定折叠特性的存在，其取决于影响病理性tau种类的行为的同种型或突变。本文的在线版本（10.1186/s40478-018-0637-7）包含补充材料，可供授权用户使用。
Tauopathies are a heterogeneous group of pathologies characterized by tau aggregation inside neurons. Most of them are sporadic but certain tauopathies rely on tau gene (MAPT) mutations. They particularly differ from one to another by their different neuropathological signatures e.g. lesion shapes, regions affected and molecular composition of aggregates. Six isoforms of tau exist, but they do not all co-aggregate in each tauopathy but rather have a unique signature for each one. In some tauopathies such as Alzheimer’s disease (AD), tau protein aggregation follows stereotypical anatomical stages. Recent data suggest that this progression is due to an active process of tau protein propagation from neuron-to-neuron. We wondered how tau isoforms or mutations could influence the process of tau aggregation and tau propagation. In human neuropathological material, we found that MAPT mutations induce a faster misfolding compared to tau found in sporadic AD patients. In the rat brain, we observed cell-to-cell transfer of non-pathological tau species irrespective of the tested isoform or presence of a mutation. By contrast, we found that the species of tau impact the propagation of tau pathology markers such as hyperphosphorylation and misfolding. Indeed, misfolding and hyperphosphorylated tau proteins do not spread at the same rate when tau is mutated, or the isoform composition is modified. These results clearly argue for the existence of specific folding properties of tau depending on isoforms or mutations impacting the behavior of pathological tau species. The online version of this article (10.1186/s40478-018-0637-7) contains supplementary material, which is available to authorized users.
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DOI：
10.1074/jbc.m114.589309
发表时间：
2015-01-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Falcon B;Cavallini A;Angers R;Glover S;Murray TK;Barnham L;Jackson S;O'Neill MJ;Isaacs AM;Hutton ML;Szekeres PG;Goedert M;Bose S
通讯作者：
Bose S
DOI：
10.1083/jcb.115.3.717
发表时间：
1991-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Butner KA;Kirschner MW
通讯作者：
Kirschner MW
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：
3.7
作者：
Dujardin S;Bégard S;Caillierez R;Lachaud C;Delattre L;Carrier S;Loyens A;Galas MC;Bousset L;Melki R;Aurégan G;Hantraye P;Brouillet E;Buée L;Colin M
通讯作者：
Colin M
影响因子：
12.4
作者：
Caillierez, Raphaelle;Begard, Severine;Colin, Morvane
通讯作者：
Colin, Morvane