Lagalwar Sarita, Guillozet-Bongaarts Angela L, Berry Robert W, Binder Lester I
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
J Neuropathol Exp Neurol. 2006 May;65(5):455-64. doi: 10.1097/01.jnen.0000229236.98124.d8.
The mitogen-activated protein (MAP) kinase SAPK/JNK phosphorylates tau protein at many of its proline-directed serine/threonine residues in vitro and is a likely candidate kinase to phosphorylate the pathologically relevant S422 site on tau. Since phosphorylation of tau, particularly at S422, is a relatively early marker of AD and seems to precede tangle formation, it appears likely that an early form of activated SAPK/JNK might be detected by immunohistochemical means around the time that tau begins to aggregate into tangles. We report here that an antibody to phospho-SAPK/JNK (p-SAPK/JNK) reacts with several types of lesions including granular bodies in limbic areas; NFTs in limbic cortex and temporal neocortex; occasional neuritic plaques in temporal neocortex; and select axons in the hippocampus, entorhinal cortex, and inferior temporal cortex. In order to characterize the appearance of granular p-SAPK/JNK and determine if it appears early in disease, we employed an immunohistochemical study of postmortem limbic tissue from 20 cases ranging from Braak stages I-VI. By co-staining with anti-tau antibodies specific to different molecular events that occur during tangle evolution, we were able to identify the appearance of p-SAPK/JNK in early Braak stages with an increased elevation during the limbic stages of AD and during the early stages of the formation of individual hippocampal tangles.
丝裂原活化蛋白（MAP）激酶应激激活蛋白激酶/应激活化蛋白激酶（SAPK/JNK）在体外可使其脯氨酸导向的丝氨酸/苏氨酸残基中的许多位点磷酸化，并且可能是使tau蛋白上与病理相关的S422位点磷酸化的候选激酶。由于tau蛋白的磷酸化，特别是在S422位点的磷酸化，是阿尔茨海默病（AD）相对早期的标志物，且似乎先于缠结形成，因此有可能在tau蛋白开始聚集成缠结时，通过免疫组织化学方法检测到早期形式的活化SAPK/JNK。我们在此报告，一种抗磷酸化SAPK/JNK（p-SAPK/JNK）抗体可与多种类型的病变发生反应，包括边缘区域的颗粒体；边缘皮质和颞叶新皮质中的神经原纤维缠结（NFTs）；颞叶新皮质中偶尔出现的神经炎斑块；以及海马体、内嗅皮质和颞下回皮质中的特定轴突。为了描述颗粒状p-SAPK/JNK的出现情况并确定其是否在疾病早期出现，我们对20例从Braak分期I至VI期的死后边缘组织进行了免疫组织化学研究。通过与针对缠结演变过程中发生的不同分子事件的抗tau抗体进行共染色，我们能够确定p-SAPK/JNK在Braak早期阶段的出现情况，在AD的边缘阶段以及单个海马体缠结形成的早期阶段其水平升高。
