Activation of the JNK/p38 pathway occurs in diseases characterized by tau protein pathology and is related to tau phosphorylation but not to apoptosis
Activation of the JNK/p38 pathway occurs in diseases characterized by tau protein pathology and is related to tau phosphorylation but not to apoptosis
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DOI：
10.1093/jnen/60.12.1190
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发表时间：
2001-12-01
影响因子：
3.2
通讯作者：
Migheli, A
中科院分区：
文献类型：
--
作者：
Atzori, C;Ghetti, B;Migheli, A
JNK和p38是MAP激酶家族中的两个成员，受到包括氧化应激在内的各种应激的强烈诱导，并参与了细胞凋亡的调节。作为这两种蛋白的体外磷酸化，我们研究了它们在一组神经退行性疾病中的免疫组织化学定位，这些疾病的特征是细胞内过度磷酸化的tau蛋白沉积，包括阿尔茨海默病、Pick病、进行性核上性瘫痪、皮质基底膜变性、Gerstmann-Straussler-Scheinker病-Indiana家系以及与17号染色体连锁的额颞叶痴呆。在所有组织样本中，都发现这两种MAP蛋白在含有tau阳性沉积的神经元或神经胶质细胞中都有很强的免疫反应。双重免疫组织化学显示JNK和p38与tau共定位于包涵体中。分析与细胞凋亡相关的变化(DNA片段化、激活的caspase-3)表明，JNK和p38的表达与细胞凋亡级联反应的激活无关。我们的数据表明，在各种异常的tau包涵体中，磷酸化的JNK和磷酸化的p38与过度磷酸化的tau相关，提示这些激酶可能在tau病理的退行性疾病的发生发展中发挥作用。
JNK and p38, two members of the MAP kinase family, are strongly induced by various stresses including oxidative stress and have been involved in regulation of apoptosis. As both kinases phosphorylate tau protein in vitro, we have investigated their immunohistochemical localization in a group of neurodegenerative diseases characterized by intracellular deposits of hyperphosphorylated tau, Cases included Alzheimer disease, Pick disease, progressive supranuclear palsy, corticobasal degeneration, Gerstmann-Straussler-Scheinker disease-Indiana kindred, and frontotemporal dementia with parkinsonism linked to chromosome 17. In all tissue samples, strong immunoreactivity for both MAP kinases was found in the same neuronal or glial cells that contained tau-positive deposits. By double immunohistochemistry, JNK and p38 colocalized with tau in the inclusions. Analysis of apoptosis-related changes (DNA fragmentation, activated caspase-3) showed that the expression of JNK and p38 was unrelated to activation of an apoptotic cascade. Our data indicate that phospho-JNK and phospho-p38 are associated with hyperphosphorylated tau in a variety of abnormal tau inclusions, suggesting that these kinases may play a role in the development of degenerative diseases with tau pathology.