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Understanding the role of glycogen synthase kinase-3 in L-DOPA-induced dyskinesia in Parkinson's disease

Title
Understanding the role of glycogen synthase kinase-3 in L-DOPA-induced dyskinesia in Parkinson's disease
Author
고성호
Keywords
Parkinson's disease; glycogen synthase kinase-3 (GSK-3); l-3; 4-dihydroxyphenylalanine (L-DOPA); neurotoxicity
Issue Date
2018-01
Publisher
TAYLOR & FRANCIS LTD
Citation
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, v. 14, no. 1, page. 83-90
Abstract
Introduction: Levodopa (L-DOPA) is the most commonly used drug for Parkinson's disease (PD), but its long-term use is associated with various complications, including L-DOPA-induced dyskinesia (LID). Many studies have suggested that L-DOPA neurotoxicity and LID are associated with glycogen synthase kinase-3 (GSK-3) activation.Areas covered: LID is caused by striatal dopamine (DA) denervation in PD and pulsatile L-DOPA treatment. These factors lead to dysregulated DA transmission, abnormal intracellular signaling and transcription factors in striatal neurons, and altered gene expression and plasticity at corticostriatal synapses. The mechanisms of L-DOPA toxicity involve oxidative stress, L-DOPA oxidation to quinone, mitochondrial dysfunction, and a-synuclein. GSK-3 has been suggested to play key roles in all the mechanisms associated of L-DOPA toxicity and LID in PD.Expert opinion: GSK-3 plays critical roles in L-DOPA-induced neurotoxicity, and the development of specific methods to inhibit GSK-3 function may help prevent L-DOPA neurotoxicity and LID in PD. However, balanced GSK-3 inhibition and less beta-catenin degradation is essential for preventing LID, because too much GSK-3 inhibition increases beta-catenin levels, which is related to cancers.
URI
https://www.tandfonline.com/doi/full/10.1080/17425255.2018.1417387http://repository.hanyang.ac.kr/handle/20.500.11754/117156
ISSN
1742-5255; 1744-7607
DOI
10.1080/17425255.2018.1417387
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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