N-Propargyl-1 (R)-aminoindan, rasagiline, increases glial cell line-derived neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of NF-kappaB transcription factor.
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 (IkappaB) of nuclear factor-kappaB (NF-kappaB), and translocation of active p65 subunit from cytoplasm into nuclei. Activation of NF-kappaB was also quantitatively determined by NF-kappaB p65 transcription assay. Sulfasalazine, an inhibitor of IkappaB kinase, suppressed the activation of NF-kappaB and the increase of GDNF by rasagiline simultaneously, further indicating the involvement of the IkappaB kinase-NF-kappaB 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.
Maruyama
Wakako
W
Department of Basic Gerontology, National Institute for Longevity Sciences, Gengo 36-3, Morioka-chio, Obu Aichi 474-8522, Japan.
Nitta
Atusmi
A
Shamoto-Nagai
Masayo
M
Hirata
Yoko
Y
Akao
Yukihiro
Y
Yodim
Moussa
M
Furukawa
Shoei
S
Nabeshima
Toshitaka
T
Naoi
Makoto
M
D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007189:Indans; D016328:NF-kappa B; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C031967:rasagiline