RGD Reference Report - Activation and redistribution of c-jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. - Rat Genome Database

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

Authors: Zhu, X  Raina, AK  Rottkamp, CA  Aliev, G  Perry, G  Boux, H  Smith, MA 
Citation: Zhu X, etal., J Neurochem. 2001 Jan;76(2):435-41.
RGD ID: 10412676
Pubmed: PMID:11208906   (View Abstract at PubMed)

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-alpha and JNK3/SAPK-beta were related to neurofibrillary pathology and JNK1/SAP-Kgamma 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 tau-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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IEP 10412676protein:increased expression:CA1 field of hippocampus:RGD 
Alzheimer's disease disease_progressionIEP 10412676protein:increased expression:brain and CA1 field of hippocampus:RGD 
Alzheimer's disease  IEP 10412676protein:increased expression:brain and CA1 field of hippocampus:RGD 
Alzheimer's disease  ISOMAPK10 (Homo sapiens)10412676; 10412676protein:increased expression:CA1 field of hippocampus:RGD 
Alzheimer's disease disease_progressionISOMAPK8 (Homo sapiens)10412676; 10412676protein:increased expression:brain and CA1 field of hippocampus:RGD 
Alzheimer's disease  ISOMAPK9 (Homo sapiens)10412676; 10412676protein:increased expression:brain and CA1 field of hippocampus:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mapk10  (mitogen activated protein kinase 10)
Mapk8  (mitogen-activated protein kinase 8)
Mapk9  (mitogen-activated protein kinase 9)

Genes (Mus musculus)
Mapk10  (mitogen-activated protein kinase 10)
Mapk8  (mitogen-activated protein kinase 8)
Mapk9  (mitogen-activated protein kinase 9)

Genes (Homo sapiens)
MAPK10  (mitogen-activated protein kinase 10)
MAPK8  (mitogen-activated protein kinase 8)
MAPK9  (mitogen-activated protein kinase 9)


Additional Information