α-Synuclein Oligomers Induce a Unique Toxic Tau Strain.
α-Synuclein Oligomers Induce a Unique Toxic Tau Strain.
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DOI：
10.1016/j.biopsych.2017.12.018
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发表时间：
2018-10-01
影响因子：
10.6
通讯作者：
Kayed R
中科院分区：
文献类型：
--
作者：
Castillo-Carranza DL;Guerrero-Muñoz MJ;Sengupta U;Gerson JE;Kayed R
α-突触核蛋白和tau聚集体在几种神经退行性疾病（包括帕金森病和阿尔茨海默病）中的共存提出了播种机制参与疾病进展的可能性。为了进一步研究α-突触核蛋白在tau聚集途径中的作用，我们使用重组和脑源性tau和α-突触核蛋白寡聚体进行了一组实验，以在体外和体内接种单体tau聚集。脑源性tau寡聚体分离自进行性核上性麻痹的充分表征的病例（n = 4），并且脑源性α-突触核蛋白/tau寡聚体的复合物分离自帕金森病患者（n = 4）。通过标准生物化学方法纯化和表征分离的结构，然后注射到Htau小鼠（n = 24）中以评估它们的毒性和在tau聚集中的作用。我们发现α-突触核蛋白诱导了一种独特的毒性tau寡聚体菌株，其避免了原纤维的形成。在体内，向Htau小鼠脑中给予帕金森病脑源性α-突触核蛋白/tau寡聚体加速了内源性tau寡聚体的形成，同时增加了细胞损失。我们的研究结果首次提供了证据，证明α-突触核蛋白增强了tau的有害作用，从而促进了疾病的进展。
The coexistence of α-synuclein and tau aggregates in several neurodegenerative disorders, including Parkinson’s disease and Alzheimer’s disease, raises the possibility that a seeding mechanism is involved in disease progression. To further investigate the role of α-synuclein in the tau aggregation pathway, we performed a set of experiments using both recombinant and brain-derived tau and α-synuclein oligomers to seed monomeric tau aggregation in vitro and in vivo. Brain-derived tau oligomers were isolated from well-characterized cases of progressive supranuclear palsy (n = 4) and complexes of brain-derived α-synuclein/tau oligomers isolated from patients with Parkinson’s disease (n = 4). The isolated structures were purified and characterized by standard biochemical methods, then injected into Htau mice (n = 24) to assess their toxicity and role in tau aggregation. We found that α-synuclein induced a distinct toxic tau oligomeric strain that avoids fibril formation. In vivo, Parkinson’s disease brain-derived α-synuclein/tau oligomers administered into Htau mouse brains accelerated endogenous tau oligomer formation concurrent with increasing cell loss. Our findings provide evidence, for the first time, that α-synuclein enhances the harmful effects of tau, thus contributing to disease progression.
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依赖性β-淀粉样蛋白引发的tau依赖性微管拆卸。
DOI：
10.1083/jcb.200605187
发表时间：
2006-11-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
King ME;Kan HM;Baas PW;Erisir A;Glabe CG;Bloom GS
通讯作者：
Bloom GS
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：
7.1
作者：
Gerson JE;Sengupta U;Lasagna-Reeves CA;Guerrero-Muñoz MJ;Troncoso J;Kayed R
通讯作者：
Kayed R
影响因子：
4.8
作者：
Bucciantini, M;Calloni, G;Stefani, M
通讯作者：
Stefani, M
影响因子：
34.7
作者：
Irwin, David J.;Lee, Virginia M. -Y.;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.