Characterization of tau oligomeric seeds in progressive supranuclear palsy.
Characterization of tau oligomeric seeds in progressive supranuclear palsy.
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DOI：
10.1186/2051-5960-2-73
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发表时间：
2014-06-14
影响因子：
7.1
通讯作者：
Kayed R
中科院分区：
文献类型：
--
作者：
Gerson JE;Sengupta U;Lasagna-Reeves CA;Guerrero-Muñoz MJ;Troncoso J;Kayed R
进行性核上性麻痹（PSP）是一种神经退行性tau蛋白病，其主要定义为tau蛋白沉积到球状型神经元缠结（NFT）中。天然形式的Tau对微管动力学具有重要功能。Tau在外显子2、3和10中经历选择性剪接，这导致六种不同的同种型。外显子10上的剪接产物最容易发生突变。三个重复（3R）和四个重复（4R）tau，像其他疾病相关的淀粉样蛋白，可以形成寡聚体，然后可以进一步聚集并形成原纤维。我们实验室和其他实验室的最新研究提供了证据，证明tau寡聚体，而不是NFT，是神经退行性tau蛋白病中毒性最大的物质，并导致tau蛋白的病理性扩散。PSP脑切片的分析揭示了球状型NFT，以及磷酸化和未磷酸化的tau寡聚体。通过蛋白质印迹和ELISA对PSP脑的分析揭示了与年龄匹配的对照脑相比tau寡聚体水平增加的存在。从PSP脑中免疫沉淀寡聚体，并能够接种3R和4R tau亚型的寡聚化。这是第一次在PSP中表征tau寡聚体。这些结果表明，tau寡聚体是PSP病理学的重要组成部分，沿着NFT。PSP脑源性tau寡聚体播种3R和4R tau的能力表明，这些寡聚体代表负责疾病传播的病理物种，并且在纯神经变性tau病变中存在寡聚体意味着在具有其他淀粉样蛋白的疾病中观察到的tau的常见神经病理过程。
Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy which is primarily defined by the deposition of tau into globose-type neurofibrillary tangles (NFT). Tau in its native form has important functions for microtubule dynamics. Tau undergoes alternative splicing in exons 2, 3, and 10 which results in six different isoforms. Products of splicing on exon 10 are the most prone to mutations. Three repeat (3R) and four repeat (4R) tau, like other disease-associated amyloids, can form oligomers which may then go on to further aggregate and form fibrils. Recent studies from our laboratory and others have provided evidence that tau oligomers, not NFTs, are the most toxic species in neurodegenerative tauopathies and seed the pathological spread of tau. Analysis of PSP brain sections revealed globose-type NFTs, as well as both phosphorylated and unphosphorylated tau oligomers. Analysis of PSP brains via Western blot and ELISA revealed the presence of increased levels of tau oligomers compared to age-matched control brains. Oligomers were immunoprecipitated from PSP brain and were capable of seeding the oligomerization of both 3R and 4R tau isoforms. This is the first time tau oligomers have been characterized in PSP. These results indicate that tau oligomers are an important component of PSP pathology, along with NFTs. The ability of PSP brain-derived tau oligomers to seed 3R and 4R tau suggests that these oligomers represent the pathological species responsible for disease propagation and the presence of oligomers in a pure neurodegenerative tauopathy implies a common neuropathological process for tau seen in diseases with other amyloid proteins.
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影响因子：
5.3
作者：
Castillo-Carranza, Diana L.;Sengupta, Urmi;Kayed, Rakez
通讯作者：
Kayed, Rakez
影响因子：
15.1
作者：
Lasagna-Reeves CA;Castillo-Carranza DL;Sengupta U;Clos AL;Jackson GR;Kayed R
通讯作者：
Kayed R
影响因子：
6
作者：
Kopeikina, Katherine J.;Carlson, George A.;Spires-Jones, Tara L.
通讯作者：
Spires-Jones, Tara L.
DOI：
10.1073/pnas.121119298
发表时间：
2001-06-05
影响因子：
11.1
作者：
Alonso, AD;Zaidi, T;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA