Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration
Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration
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DOI：
10.1002/ana.10793
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发表时间：
2004-01-01
影响因子：
11.2
通讯作者：
Mochizuki, A
中科院分区：
文献类型：
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作者：
Arai, T;Ikeda, K;Mochizuki, A
进行性核上性麻痹（PSP）和皮质基底变性（CBD）是神经退行性疾病，其特征是细胞浆内过度磷酸化tau蛋白聚集，具有四个微管结合重复序列。虽然PSP和CBD具有不同的病理特征，但尚未发现聚集tau的生化差异。在本研究中，我们检查了8例PSP患者，6例CBD患者和1例具有CBD和PSP病理特征的非典型患者的大脑。在萨科齐不溶性脑提取物的免疫印迹上，PSP的低分子量tau片段以33kDa条带为主，而CBD则以两个密切相关的约37kDa条带为主。非典型病例的免疫印迹同时显示33kDa条带和37kDa双链。蛋白测序和免疫化学分析表明，33kDa带和37kDa双链由tau蛋白的羧基一半组成，具有不同的氨基末端。这些结果表明，尽管tau亚型的组成相同，但在这两种疾病中异常tau的蛋白水解过程不同。这种生化差异可能与这些疾病的神经病理特征有关。
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative diseases that are characterized by intracytoplasmic aggregates of hyperphosphorylated tau with four microtubule-binding repeats. Although PSP and CBD have distinctive pathological features, no biochemical difference in aggregated tau has been identified. In this study, we examined the brains of eight patients with PSP, six patients with CBD, and one atypical case with pathological features of both CBD and PSP. On immunoblots of sarkosyl-insoluble brain extracts, a 33kDa band predominated in the low molecular weight tau fragments in PSP, whereas two closely related bands of approximately 37kDa predominated in CBD. Immunoblots of the atypical case showed both the 33kDa band and the 37kDa doublet. Protein sequencing and immunochemical analyses showed that the 33kDa band and the 37kDa doublet consisted of the carboxyl half of tau with different amino termini. These results suggest that, despite the identical composition of tau isoforms, different proteolytic processing of abnormal tau takes place in these two diseases. Such a biochemical divergence may be related to the neuropathological features of these diseases.