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c‐Jun phosphorylation in Alzheimer disease
Author(s) -
Thakur Akanksha,
Wang Xinglong,
Siedlak Sandra L.,
Perry George,
Smith Mark A.,
Zhu Xiongwei
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21298
Subject(s) - c jun , phosphorylation , immunostaining , kinase , neurofibrillary tangle , apoptosis , tunel assay , biology , programmed cell death , microbiology and biotechnology , hippocampal formation , cytoplasm , alzheimer's disease , transcription factor , neuroscience , pathology , immunohistochemistry , medicine , gene , disease , immunology , biochemistry , senile plaques
The c‐Jun N‐terminal kinase (JNK) pathway is known to be activated by oxidative stress and can lead to either defensive‐protective adaptations in the cell or apoptosis. The JNK pathway is activated in Alzheimer disease (AD), as demonstrated in studies showing higher levels of phospho‐JNK in affected neurons in AD brains than in controls. c‐Jun, a transcription factor, is the downstream effector of JNK, whose activation requires phosphorylation of Ser63/Ser73. In this study, we characterized and compared the localization of c‐Jun phosphorylated at either Ser63 or Ser73 in the hippocampi of AD cases with that in age‐matched controls. Phospho‐c‐Jun (Ser73) was found to be strongly associated with neurofibrillary tangles and granulovacuolar degeneration (GVD) in addition to the nuclei in neurons in the hippocampal regions of the AD brain, but was virtually absent in most controls. Phospho‐c‐Jun (Ser63) was also found to be associated with GVD in AD brains. Indeed, phospho‐c‐Jun (Ser73) immunostaining was much more extensive than that of phospho‐c‐Jun (Ser63), with all the phospho‐c‐Jun (Ser63)–positive neurons also being phospho‐c‐Jun (Ser73) positive. Significant overlap between phospho‐c‐Jun and phospho‐JNK suggested a mechanistic link. In addition, the neurons showing increased levels of phospho‐c‐Jun (Ser73) in the cytoplasmic GVD were negative for TUNEL, suggesting a mechanism protecting the cells from death. Overall, this study demonstrated specific alterations in c‐Jun phosphorylation and distribution in AD which is not necessarily linked to apoptosis but rather may represent an adaptation process in the face of oxidative stress. © 2007 Wiley‐Liss, Inc.