Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation.
Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation.
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DOI：
10.1007/s00401-013-1080-2
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发表时间：
2013-04
影响因子：
12.7
通讯作者：
Seeley WW
中科院分区：
文献类型：
--
作者：
Grinberg LT;Wang X;Wang C;Sohn PD;Theofilas P;Sidhu M;Arevalo JB;Heinsen H;Huang EJ;Rosen H;Miller BL;Gan L;Seeley WW
翻译后修饰在tau蛋白聚集和相关神经变性中起关键作用。由于过度磷酸化本身并不一定会导致tau蛋白聚集，因此最近已经探索了其他翻译后修饰。Tau乙酰化促进聚集并抑制Tau稳定微管的能力。最近的研究表明，在AD和一些4R tau蛋白病中，乙酰化和磷酸化tau蛋白共定位。我们开发了一种新的单克隆抗体对乙酰化的tau在赖氨酸残基274，它识别3R和4R tau，并使用免疫组织化学和免疫荧光探针22例，包括AD和另外8个家族性或散发性tau蛋白病。在除嗜银粒病（AGD）之外的所有tau蛋白病中鉴定出乙酰化tau蛋白。AGD是一种与年龄相关的常见但非典型的4R tau蛋白病，并不总是与临床进展相关。在病理学上，AGD的特征在于神经胶质细胞颗粒、前神经胶质细胞缠结和少突胶质细胞卷曲体，所有这些都被磷酸化tau抗体识别。这些内含物中缺乏乙酰化tau表明AGD代表了一种独特的tau蛋白病。我们的数据与以前的研究结果一致，提出了AGD可以对AD相关tau病理学的传播起保护作用的假设。Tau乙酰化作为tau毒性增殖的关键修饰值得进一步研究。
Post-translational modifications play a key role in tau protein aggregation and related neurodegeneration. Because hyperphosphorylation alone does not necessarily cause tau aggregation, other post-translational modifications have been recently explored. Tau acetylation promotes aggregation and inhibits tau’s ability to stabilize microtubules. Recent studies have shown co-localization of acetylated and phosphorylated tau in AD and some 4R tauopathies. We developed a novel monoclonal antibody against acetylated tau at lysine residue 274, which recognizes both 3R and 4R tau, and used immunohistochemistry and immunofluorescence to probe 22 cases, including AD and another eight familial or sporadic tauopathies. Acetylated tau was identified in all tauopathies except argyrophilic grain disease (AGD). AGD is an age-associated, common but atypical 4R tauopathy, not always associated with clinical progression. Pathologically, AGD is characterized by neuropil grains, pre-neurofibrillary tangles, and oligodendroglial coiled bodies, all recognized by phospho-tau antibodies. The lack of acetylated tau in these inclusions suggests that AGD represents a distinctive tauopathy. Our data converge with previous findings to raise the hypothesis that AGD could play a protective role against the spread of AD-related tau pathology. Tau acetylation as a key modification for the propagation tau toxicity deserves further investigation.
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影响因子：
11.4
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
16.2
作者：
LEE, G;NEVE, RL;KOSIK, KS
通讯作者：
KOSIK, KS
影响因子：
16.2
作者：
Min, Sang-Won;Cho, Seo-Hyun;Zhou, Yungui;Schroeder, Sebastian;Haroutunian, Vahram;Seeley, William W.;Huang, Eric J.;Shen, Yong;Masliah, Eliezer;Mukherjee, Chandrani;Meyers, David;Cole, Philip A.;Ott, Melanie;Gan, Li
通讯作者：
Gan, Li
影响因子：
3.3
作者：
Goode, BL;Denis, PE;Feinstein, SC
通讯作者：
Feinstein, SC