Journal article
JNK activation is associated with intracellular β-amyloid accumulation
Brain research. Molecular brain research, v 85(1)
2000
PMID: 11146125
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
c-Jun has been implicated in the pathogenesis of Alzheimer’s disease (AD), but the upstream cascade leading to c-Jun activation in AD is not known. Activation of c-Jun N-terminal kinase (JNK) is obviously a candidate for the upstream event. We tested this possibility focusing on PS1-linked AD. First, we observed that JNK is actually activated in cerebral neurons of PS1-linked AD patients, using immunohistochemistry and Western blot analyses with anti-activated JNK antibodies. We analyzed the relationship between β-amyloid (βA) and JNK activation by using aged transgenic mice overexpressing mutant (M146L) PS1 and human AD brains. The mice showed no neuronal loss but a very few diffuse βA deposits, corresponding to the early stage of PS1-linked AD brain. Some neurons were reactive for anti-βA antibodies in the cerebral cortex. Interestingly, JNK activation was observed in neurons showing intracellular βA immunoreactivity in transgenic mice. Association between intracellular βA and JNK activation was confirmed in cortical neurons of sporadic and PS1-linked AD patients. Furthermore, introduction of βA peptides into the primary culture cortical neurons induced JNK activation and cell death. Collectively, these results suggested that intracellular βA accumulation might trigger JNK activation leading to neuronal death.
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Details
- Title
- JNK activation is associated with intracellular β-amyloid accumulation
- Creators
- Mikio Shoji - Toyama Pharmaceutical Co. 2-4-1, Shimo-okui, Toyama 930-8508, Japan.Noboru Iwakami - Toyama Pharmaceutical Co. 2-4-1, Shimo-okui, Toyama 930-8508, Japan.Sousuke Takeuchi - University of TokyoMasaaki Waragai - University of TokyoMisao Suzuki - Kumamoto UniversityIchiro Kanazawa - University of TokyoCarol F. Lippa - Hahnemann University HospitalSatoshi Ono - Toyama Pharmaceutical Co. 2-4-1, Shimo-okui, Toyama 930-8508, Japan.Hitoshi Okazawa - University of Tokyo
- Publication Details
- Brain research. Molecular brain research, v 85(1)
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000166432600025
- Scopus ID
- 2-s2.0-0034727889
- Other Identifier
- 991019312466004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences