Activation and redistribution of c-Jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease

Xiongwei Zhu, Arun K. Raina, Catherine Rottkamp, Gjumrakch Aliev, George Perry, Heather Boux, Mark A. Smith

Research output: Contribution to journalArticle

320 Citations (Scopus)

Abstract

Cellular responses to increased oxidative stress appear to be a mechanism that contributes to the varied cytopathology of Alzheimer's disease (AD). In this regard, we suspect that c-Jun N-terminal kinase/Stress activated protein kinase (JNK/SAPK), a major cellular stress response protein induced by oxidative stress, plays an important role in Alzheimer disease in susceptible neurons facing the dilemma of proliferation or death. We found that JNK2/SAPK-α and JNK3/SAPK-β were related to neurofibrillary pathology and JNK1/SAP-Kγ related to Hirano bodies in cases of AD but were only weakly diffuse in the cytoplasm in all neurons in control cases and in non-involved neurons in diseased brain. In this regard, in hippocampal and cortical regions of individuals with severe AD, the activated phospho-JNK/SAPK was localized exclusively in association with neurofibrillar alterations including neurofibrillary tangles, senile plaque neurites, neuropil threads and granulovacuolar degeneration structures (GVD), completely overlapping with τ-positive neurofibrillary pathology, but was virtually absent in these brain regions in younger and age-matched controls without pathology. However, in control patients with some pathology, as well as in mild AD cases, there was nuclear phospho-JNK/SAPK and translocation of phospho-JNK/SAPK from nuclei to cytoplasm, respectively, indicating that the activation and re-distribution of JNK/SAPK correlates with the progress of the disease. By immunoblot analysis, phospho-JNK/SAPK is significantly increased in AD over control cases. Together, these findings suggest that JNK/SAPK dysregulation, probably resulting from oxidative stress, plays an important role in the increased phosphorylation of cytoskeletal proteins found in AD.

Original languageEnglish (US)
Pages (from-to)435-441
Number of pages7
JournalJournal of Neurochemistry
Volume76
Issue number2
DOIs
StatePublished - Feb 5 2001
Externally publishedYes

Fingerprint

JNK Mitogen-Activated Protein Kinases
Heat-Shock Proteins
Protein Kinases
Neurons
Alzheimer Disease
Chemical activation
Phosphotransferases
Pathology
Oxidative stress
Oxidative Stress
Brain
Cytoplasm
Neuropil Threads
Neurofibrillary Tangles
Phosphorylation
Cytoskeletal Proteins
Amyloid Plaques
Brain Diseases
Neurites
Protein Transport

Keywords

  • Alzheimer's disease
  • Cytoskeleton
  • Oxidative stress
  • Phosphorylation
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Activation and redistribution of c-Jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. / Zhu, Xiongwei; Raina, Arun K.; Rottkamp, Catherine; Aliev, Gjumrakch; Perry, George; Boux, Heather; Smith, Mark A.

In: Journal of Neurochemistry, Vol. 76, No. 2, 05.02.2001, p. 435-441.

Research output: Contribution to journalArticle

Zhu, Xiongwei ; Raina, Arun K. ; Rottkamp, Catherine ; Aliev, Gjumrakch ; Perry, George ; Boux, Heather ; Smith, Mark A. / Activation and redistribution of c-Jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. In: Journal of Neurochemistry. 2001 ; Vol. 76, No. 2. pp. 435-441.
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