title: Role of glycogen synthase kinase-3 in l-DOPA-induced neurotoxicity.
abstract: l-DOPA is the gold standard for the treatment of Parkinson's disease. Despite the obvious benefits of l-DOPA treatment, a potential drawback of such a treatment is its potential for neurotoxicity. The best-known potential mechanisms of l-DOPA toxicity involve oxidative stress, including nitrosative stress and increased generation of neurotoxins, oxidation of l-DOPA to quinone and semiquinone, mitochondrial dysfunction and genomic DNA damage. On the other hand, it has also been reported that l-DOPA is not neurotoxic, but rather neuroprotective. Although there are many studies on the neurotoxicity of l-DOPA, a debate regarding its effect on neuronal cells still remains. Glycogen synthase kinase-3 (GSK-3) affects a diverse range of biological functions controlling gene expression, cellular architecture and apoptosis. Recently, important roles of GSK-3 in l-DOPA neurotoxicity have been suggested by studies using an endoplasmic reticulum-stressed Parkinson's disease model. In this review, we focus our discussion on the following topics: i) l-DOPA neurotoxicity; ii) the role of GSK-3 in neuronal cell death; iii) the role of GSK-3 in l-DOPA neurotoxicity; and iv) the development of new GSK-3 inhibitors.
authors: Hanyang University College of Medicine, Department of Neurology, Seongdong-gu, Seoul, Korea.
authors: Seong-Ho
authors: SH
authors: Koh
authors: Seung Hyun
authors: SH
authors: Kim
authors: Hee-Tae
authors: HT
authors: Kim
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000633:toxicity*; D016923:Cell Death / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000633:toxicity*; D009474:Neurons / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000201:enzymology* / Q000235:genetics*
chemical_list: D000978:Antiparkinson Agents; D004791:Enzyme Inhibitors; D007980:Levodopa; D038362:Glycogen Synthase Kinase 3