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• W1988146449 abstract "l-dopa is a precursor for dopamine synthesis and a mainstay treatment for Parkinson's disease. However, l-dopa therapy is not without side effects that may be attributed to non-dopaminergic mechanisms. Synthesized dopamine can be neurotoxic through its enzymatic degradation by monoamine oxidase (MAO) to form the reactive byproduct, hydrogen peroxide and hydroxyl radicals or through auto-oxidation to form highly reactive quinones that can bind proteins and render them non-functional. Since l-dopa could be decarboxylated by aromatic amino acid decarboxylase (AADC) present within both dopamine and serotonin neurons, it was hypothesized that serotonin neurons convert l-dopa into dopamine to generate excessive reactive oxygen species and quinoproteins that ultimately lead to serotonin neuron death. To examine the effects of l-dopa on serotonin neurons, the RN46A-B14 cell line was used. These immortalized serotonergic cell cultures were terminally differentiated and then incubated with varying concentrations of l-dopa. Results show that RN46A-B14 cells contain AADC and can synthesize dopamine after incubation with l-dopa. Furthermore, l-dopa dose-dependently increased intracellular reactive oxygen species (ROS) and cell death. Dopamine, ROS production and cell death were attenuated by co-incubation with the AADC inhibitor, NSD-1015. The MAO inhibitor, pargyline, also attenuated cell death and ROS after l-dopa treatment. Lastly, quinoprotein formation was enhanced significantly by incubation with l-dopa. Taken together, these data illustrate that serotonergic cells can produce dopamine and that the accumulation of dopamine after l-dopa and its subsequent degradation can lead to ROS production and death of RN46A-B14 serotonergic cells." @default.
• W1988146449 created "2016-06-24" @default.
• W1988146449 creator A5042693752 @default.
• W1988146449 creator A5049960558 @default.
• W1988146449 date "2013-04-01" @default.
• W1988146449 modified "2023-10-16" @default.
• W1988146449 title "l-dopa-induced dopamine synthesis and oxidative stress in serotonergic cells" @default.
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• W1988146449 doi "https://doi.org/10.1016/j.neuropharm.2012.11.010" @default.
• W1988146449 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3638241" @default.
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