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- W1918125126 abstract "We have studied the mechanisms of auditory hair cell death after insults in vitro and in vivo . We show DNA fragmentation of hair cell nuclei after ototoxic drug and intense noise trauma. By using phospho-specific c-Jun-N-terminal kinase (JNK) and c-Jun antibodies in immunohistochemistry, we show that the JNK pathway, associated with stress, injury, and apoptosis, is activated in hair cells after trauma. CEP-1347, a derivative of the indolocarbazole K252a, is a small molecule that has been shown to attenuate neurodegeneration by blocking the activation of JNK (Maroney et al., 1998). Subcutaneously delivered CEP-1347 attenuated noise-induced hearing loss. The protective effect was demonstrated by functional tests, which showed less hearing threshold shift in CEP-1347-treated than in nontreated guinea pigs, and by morphometric methods showing less hair cell death in CEP-1347-treated cochleas. In organotypic cochlear cultures, CEP-1347 prevented neomycin-induced hair cell death. In addition to hair cells, CEP-1347 promoted survival of dissociated cochlear neurons. These results suggest that therapeutic intervention in the JNK signaling cascade, possibly by using CEP-1347, may offer opportunities to treat inner ear injuries." @default.
- W1918125126 created "2016-06-24" @default.
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- W1918125126 date "2000-01-01" @default.
- W1918125126 modified "2023-10-10" @default.
- W1918125126 title "Rescue of Hearing, Auditory Hair Cells, and Neurons by CEP-1347/KT7515, an Inhibitor of c-Jun N-Terminal Kinase Activation" @default.
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- W1918125126 doi "https://doi.org/10.1523/jneurosci.20-01-00043.2000" @default.
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