Hypersialylation is a common feature of neurofibrillary tangles and granulovacuolar degenerations in Alzheimer's disease and tauopathy brains
Hypersialylation is a common feature of neurofibrillary tangles and granulovacuolar degenerations in Alzheimer's disease and tauopathy brains
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DOI：
10.1111/neup.12277
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发表时间：
2016-08-01
期刊：
影响因子：
2.3
通讯作者：
Ikeda, Yoshio
中科院分区：
文献类型：
--
作者：
Nagamine, Shun;Yamazaki, Tsuneo;Ikeda, Yoshio
糖基化是蛋白质主要的翻译后修饰之一。在这项研究中，研究了各种神经退行性疾病的神经病理特征的唾液酸化状态。在这里，我们报告了两个含有与阿尔茨海默病(AD)相关的结构的磷酸化tau(p-tau)的新发现，即神经原纤维缠结(NFTs)和颗粒泡变性(GVD)。用抗唾液酸(SA)抗体进行免疫组织化学染色，清晰地显示AD大鼠海马区老年斑(SP)的NFT、GVD和营养不良轴突。相反，SPS的淀粉样蛋白核心根本没有被唾液酸化。有趣的是，其他含有p-tau的结构，即进行性核上性麻痹和Pick小体中的球状NFT，以及额颞叶变性和Pick小体中气球状的神经元，也被超唾液酸化。与tau病不同的是，其他神经退行性疾病的特征，如帕金森病中的路易小体、多系统萎缩中的胶质细胞质包涵体、布尼娜小体、肌萎缩侧索硬化症中的角蛋白样包涵体和圆形包涵体、神经元核内包涵体疾病中的核内包涵体以及生理小体或颗粒(脂褐素颗粒、淀粉体和黑色素颗粒)，均未被抗SA抗体标记。由于这种抗体专门识别NFT和GVD，唾液酸化免疫染色是在诊断环境中筛选这些结构的有用工具。这些结果清楚地表明，各种tau病的病理特征通常是过度唾液酸化的，唾液酸化在AD和其他tau病的p-tau积聚过程中起着重要作用。
Glycosylation is one of the major post-translational modifications of proteins. The status of sialylation of the neuropathological hallmarks of various neurodegenerative disorders was investigated in this study. Here, we report the novel findings that two phosphorylated tau (p-tau)containing structures associated with Alzheimer's disease (AD), that is, neurofibrillary tangles (NFTs) and granulovacuolar degenerations (GVDs), were hypersialylated. The NFTs, GVDs and dystrophic neurites of senile plaques (SPs) in AD hippocampi were clearly visualized by immunohistochemistry using an anti-sialic acid (SA) antibody. In contrast, the amyloid core of SPs was not sialylated at all. Interestingly, other p-tau-containing structures, that is, globose-type NFTs in progressive supranuclear palsy and Pick bodies and ballooned neurons in frontotemporal lobar degeneration with Pick bodies, were also hypersialylated. Unlike the p-tau-containing structures observed in tauopathies, the hallmarks of other neurodegenerative disorders, such as Lewy bodies in Parkinson's disease, glial cytoplasmic inclusions in multiple system atrophy, Bunina bodies, skein-like inclusions and round inclusions in amyotrophic lateral sclerosis, intranuclear inclusions in neuronal intranuclear inclusion disease and physiological bodies or granules (lipofuscin granules, corpora amylacea and melanin granules), were not immunolabeled by the anti-SA antibody. Because this antibody specifically identified NFTs and GVDs, immunostaining for sialylation represents a useful tool to screen these structures in a diagnostic setting. These results clearly indicate that the pathological hallmarks of various tauopathies are commonly hypersialylated, and that sialylation plays an important role in the process of p-tau accumulation in AD and other tauopathies.