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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)393-400
Number of pages8
JournalNeurochemistry International
Volume44
Issue number6
DOIs
Publication statusPublished - 01-01-2004
Externally publishedYes

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Glial Cell Line-Derived Neurotrophic Factor
Neuroblastoma
Transcription Factors
Dopaminergic Neurons
Parkinson Disease
Phosphotransferases
Sulfasalazine
Neuroprotective Agents
Neurodegenerative Diseases
Alzheimer Disease
Cytoplasm
Animal Models
Phosphorylation
Neurons
Messenger RNA
1-aminoindan
rasagiline
N-propargyl
3'-(1-butylphosphoryl)adenosine
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Maruyama, Wakako ; Nitta, Atusmi ; Shamoto-Nagai, Masayo ; Hirata, Yoko ; Akao, Yukihiro ; Yodim, Moussa ; Furukawa, Shoei ; Nabeshima, Toshitaka ; Naoi, Makoto. / 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. In: Neurochemistry International. 2004 ; Vol. 44, No. 6. pp. 393-400.
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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. / Maruyama, Wakako; Nitta, Atusmi; Shamoto-Nagai, Masayo; Hirata, Yoko; Akao, Yukihiro; Yodim, Moussa; Furukawa, Shoei; Nabeshima, Toshitaka; Naoi, Makoto.

In: Neurochemistry International, Vol. 44, No. 6, 01.01.2004, p. 393-400.

Research output: Contribution to journalArticle

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AU - Nitta, Atusmi

AU - Shamoto-Nagai, Masayo

AU - Hirata, Yoko

AU - Akao, Yukihiro

AU - Yodim, Moussa

AU - Furukawa, Shoei

AU - Nabeshima, Toshitaka

AU - Naoi, Makoto

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