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American Journal of Alzheimer's Disease and Other Dementias logoLink to American Journal of Alzheimer's Disease and Other Dementias
. 2002 Mar-Apr;17(2):79–88. doi: 10.1177/153331750201700209

The JNK/c-Jun cascade and Alzheimer's disease

Hitohi Okazawa 1, Steven Estus 2
PMCID: PMC10833950  PMID: 11954673

Abstract

Emerging evidence indicates that the JNK/c-Jun cascade is activated in neurons of the Alzheimer's disease brain and suggests its involvement in abnormal processes, ranging from tau phosphorylation to neuronal death. Substantial new data have accumulated on the functional relevance of causative genes in familial Alzheimer's disease and the pathological processes that occur within neurons. In this review, we summarize reported findings of the JNK/c-Jun cascade in Alzheimer's disease and discuss the relationship between the cascade and other pathological processes. We suggest that the effort to connect amyloid deposition with intracellular activation of the JNK/c-Jun cascade may modify the amyloid theory of Alzheimer's disease. Therapeutic approaches targeting the JNK/c-Jun cascade and other signaling may complement therapeutic strategies directed at reducing amyloid deposition.

Keywords: Alzheimer's disease, amyloid, CDK5, cell death, c-Jun, c-Jun N-terminal kinase (JNK), GSK-3, neuron, phosphorylation, presenilin, SAPK, tau, transcription

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Contributor Information

Hitohi Okazawa, Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Molecular Therapeutics, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.

Steven Estus, Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky.

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