N-Propargyl-1 (R)-aminoindan, rasagiline, increases glial cell line-derived neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of NF-κB transcription factor

Wakako Maruyama, Atusmi Nitta, Masayo Shamoto-Nagai, Yoko Hirata, Yukihiro Akao, Moussa Yodim, Shoei Furukawa, Toshitaka Nabeshima, Makoto Naoi

研究成果: Article

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N-Propargyl-l(R)-aminoindan, rasagiline, an anti-Parkinson drug, was found to increase the protein and mRNA levels of glial cell line-derived neurotrophic factor (GDNF) in human neuroblastoma SH-SY5Y cells, whereas an analogue without a propargyl residue, aminoindan, did not. GDNF is known to protect dopaminergic neurons in animal and cellular models of Parkinson's disease, and the supplement has been tried for the treatment of degenerating dopamine neurons in Parkinsonian patients. In this paper, intracellular mechanism underlying the induction of GDNF was studied. Rasagiline induced phosphorylation of inhibitory subunit (IκB) of nuclear factor-κB (NF-κB), and translocation of active p65 subunit from cytoplasm into nuclei. Activation of NF-κB was also quantitatively determined by NF-κB p65 transcription assay. Sulfasalazine, an inhibitor of IκB kinase, suppressed the activation of NF-κB and the increase of GDNF by rasagiline simultaneously, further indicating the involvement of the IκB kinase-NF-κB pathway. The results on the activation of the transcription factor by rasagiline are discussed in relation to its possible application as a neuroprotective drug to halt declining of neurons in neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases.

元の言語English
ページ(範囲)393-400
ページ数8
ジャーナルNeurochemistry International
44
発行部数6
DOI
出版物ステータスPublished - 05-2004
外部発表Yes

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All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

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