Discovery of a novel compound: Insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death

Yuzo Nakagawa-Yagi, Dong Kug Choi, Nobuo Ogane, Shin Ichi Shimada, Motohide Seya, Takashi Momoi, Takashi Ito, Yoshiyuki Sakaki

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

The exposure of humans and experimental animals to certain industrial toxins such as acrylamide is known to cause nerve damage classified as axonopathy, but the mechanisms involved are poorly understood. Here we show that acrylamide induces morphological changes and tyrosine phosphorylation of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), a member of the FAK subfamily, in human differentiating neuroblastoma SH-SY5Y cells. Furthermore, we identified a novel molecule designated 'compound-1' that inhibits the morphological and biochemical events. Daily oral administrations of the compound also effectively alleviated behavioral deficits in animals elicited by acrylamide in inclined plane testing, landing foot spread testing and rota-rod performance testing. The compound also effectively inhibited the biological and biochemical responses caused by another axonopathy inducer, colchicine, including tyrosine phosphorylation of Pyk2, formation of an 85-kDa poly(ADP-ribose)polymerase (PARP) fragment and apoptosis-associated induction of the NAPOR gene as well as neuronal cell death. Our findings not only provide insight into FAK and Pyk2 functions in neuronal cells, but may also be important in the development of therapeutic agents for peripheral neuropathy and neurodegeneration

Original languageEnglish
Pages (from-to)8-19
Number of pages12
JournalBrain Research
Volume909
Issue number1-2
DOIs
Publication statusPublished - Aug 3 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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