Comparative neuroprotective effects of rasagiline and aminoindan with selegiline on dexamethasone-induced brain cell apoptosis.
 

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04-23-09 08:53 AM
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Comparative neuroprotective effects of rasagiline and aminoindan with selegiline on dexamethasone-induced brain cell apoptosis.
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Comparative neuroprotective effects of rasagiline and aminoindan with selegiline on dexamethasone-induced brain cell apoptosis.

Neurotox Res. 2009 Apr;15(3):284-90

Authors: Tazik S, Johnson S, Lu D, Johnson C, Youdim MB, Stockmeier CA, Ou XM

Stress can affect the brain and lead to depression; however, the molecular pathogenesis is unclear. An association between stress and stress-induced hypersecretion of glucocorticoids occurs during stress. Dexamethasone (a synthetic glucocorticoid steroid) has been reported to induce apoptosis and increase the activity of monoamine oxidase (MAO) (Youdim et al. 1989). MAO is an enzyme for the degradation of aminergic neurotransmitters; dopamine, noradrenaline and serotonin and dietary amines and MAO inhibitors are classical antidepressant drugs. In this study, we have compared the ability of rasagiline (Azilect) and its main metabolite, R-aminoindan with selegiline (Deprenyl) in prevention of dexamethasone-induced brain cell death employing human neuroblastoma SH-SY5Y cells and glioblastoma 1242-MG cells. Dexamethasone reduced cell viability as measured by MTT test, but rasagiline, selegiline, and 1-R-aminoindan could significantly prevent dexamethasone-induced brain cell death. Among three drugs, rasagiline had the highest neuroprotective effect. Furthermore, the inhibitory effects of these drugs on MAO B catalytic activity and on apoptotic DNA damage (TUNEL staining) were examined. Rasagiline exhibited highest inhibition on MAO B enzymatic activity and prevention on DNA damage as compared to selegiline and 1-R-aminoindan. In summary, the greater neuroprotective effect of rasagiline may be associated with the combination of the parent drug and its metabolite 1-R-aminoindan.

PMID: 19384601 [PubMed - in process]