ArticleJournal of molecular neuroscience : MN2015
Indirubin-3-Oxime Effectively Prevents 6OHDA-Induced Neurotoxicity in PC12 Cells via Activating MEF2D Through the Inhibition of GSK3β.
Article in Journal of molecular neuroscience : MN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Fighting Against the Clock: Circadian Disruption and Parkinson's Disease.Journal of movement disorders · 2024Article
- The Role of MEF2 Transcription Factor Family in Neuronal Survival and Degeneration.International journal of molecular sciences · 2023Review
- Altered expression of miR-29a-3p and miR-34a-5p by specific inhibition of GSK3β in the MPPNon-coding RNA research · 2022Article
- Parkinson's Disease Master Regulators on Substantia Nigra and Frontal Cortex and Their Use for Drug Repositioning.Molecular neurobiology · 2021Article
- Lithium and Therapeutic Targeting of GSK-3.Cells · 2021Review
- Functions of Small Organic Compounds that Mimic the HNK-1 Glycan.International journal of molecular sciences · 2020Article
- Neuroprotection Against MPPFrontiers in pharmacology · 2018Article
- A Novel Tetramethylpyrazine Derivative Prophylactically Protects against Glutamate-Induced Excitotoxicity in Primary Neurons through the Blockage ofFrontiers in pharmacology · 2018Article
- Indirubin-3-Oxime Prevents HCellular and molecular neurobiology · 2017Article
- MEF2D Mediates the Neuroprotective Effect of Methylene Blue Against Glutamate-Induced Oxidative Damage in HT22 Hippocampal Cells.Molecular neurobiology · 2017Article
- Indirubin Derivative 7-Bromoindirubin-3-Oxime (7Bio) Attenuates Aβ Oligomer-Induced Cognitive Impairments in Mice.Frontiers in molecular neuroscience · 2017Article
- Fucoxanthin, a Marine Carotenoid, AttenuatesOxidative medicine and cellular longevity · 2017Article
- Fucoxanthin prevents HFood & nutrition research · 2017Article
- Re-Cloning the N27 Dopamine Cell Line to Improve a Cell Culture Model of Parkinson's Disease.PloS one · 2016Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Indirubin-3-oxime (I3O), a synthetic derivative of indirubin, was originally designed as potent inhibitors of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β) for leukemia therapy. In the current study, we have shown, for the first time, that I3O prevented 6-hydroxydopamine (6OHDA)-induced neuronal apoptosis and intracellular reactive oxygen species accumulation in PC12 cells in a concentration-dependent manner. GSK3β inhibitors but not CDK5 inhibitors reduced the neurotoxicity induced by 6OHDA. Moreover, the activation of GSK3β was observed after 6OHDA treatment. Furthermore, 6OHDA substantially decreased the transcriptional activity of myocyte enhancer factor 2D (MEF2D), a transcription factor that plays an important role in dopaminergic neuron survival, and reduced nuclear localized MEF2D expression. Interestingly, indirubin-3-oxime and GSK3β inhibitors prevented 6OHDA-induced dysregulation of MEF2D. In addition, short hairpin RNA-mediated decrease of MEF2D expression significantly abolished the neuroprotective effects of indirubin-3-oxime. Collectively, our results strongly suggested that indirubin-3-oxime prevented 6OHDA-induced neurotoxicity via activating MEF2D, possibly through the inhibition of GSK3β. In view of the capability of indirubin-3-oxime to cross the blood-brain barrier, our findings further indicated that indirubin-3-oxime might be a novel drug candidate for neurodegenerative disorders, including Parkinson's disease in particular.
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