ArticleThe Journal of biological chemistry2013
Perturbation of transcription factor Nur77 expression mediated by myocyte enhancer factor 2D (MEF2D) regulates dopaminergic neuron loss in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Towards a unified molecular mechanism for ligand-dependent activation of NR4A-RXR heterodimers.eLife · 2026Article
- MEF2D impairs mitochondrial respiration, glucose-stimulated insulin secretion, and survival in INS-1 β-cells.bioRxiv : the preprint server for biology · 2026Article
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Functional Changes Associated With the Subcellular Localization of the Nuclear Receptor NR4A1.Biochemistry research international · 2025Review
- Noncanonical contribution of microglial transcription factor NR4A1 to post-stroke recovery through TNF mRNA destabilization.PLoS biology · 2023Article
- Article
- Focusing on cyclin-dependent kinases 5: A potential target for neurological disorders.Frontiers in molecular neuroscience · 2022Review
- MiR-421 Aggravates Neurotoxicity and Promotes Cell Death in Parkinson's Disease Models by Directly Targeting MEF2D.Neurochemical research · 2021Article
- Progress and Promise of Nur77-based Therapeutics for Central Nervous System Disorders.Current neuropharmacology · 2021Review
- The nuclear receptor 4A family members: mediators in human disease and autophagy.Cellular & molecular biology letters · 2020Review
- Loss of Mef2D function enhances TLR induced IL-10 production in macrophages.Bioscience reports · 2020Article
- Article
- MEF-2 isoforms' (A-D) roles in development and tumorigenesis.Oncotarget · 2019Review
- Regulatory role of calpain in neuronal death.Neural regeneration research · 2018Review
- Neuroprotection Against MPPFrontiers in pharmacology · 2018Article
- MEF2D Mediates the Neuroprotective Effect of Methylene Blue Against Glutamate-Induced Oxidative Damage in HT22 Hippocampal Cells.Molecular neurobiology · 2017Article
- Nuclear receptor 4A (NR4A) family - orphans no more.The Journal of steroid biochemistry and molecular biology · 2016Article
- Trans effects of chromosome aneuploidies on DNA methylation patterns in human Down syndrome and mouse models.Genome biology · 2015Article
- 17β-estradiol delays 6-OHDA-induced apoptosis by acting on Nur77 translocation from the nucleus to the cytoplasm.Neurotoxicity research · 2014Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
We have earlier reported the critical nature of calpain-CDK5-MEF2 signaling in governing dopaminergic neuronal loss in vivo. CDK5 mediates phosphorylation of the neuronal survival factor myocyte enhancer factor 2 (MEF2) leading to its inactivation and loss. However, the downstream factors that mediate MEF2-regulated survival are unknown. Presently, we define Nur77 as one such critical downstream survival effector. Following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in vivo, Nur77 expression in the nigrostriatal region is dramatically reduced. This loss is attenuated by expression of MEF2. Importantly, MEF2 constitutively binds to the Nur77 promoter in neurons under basal conditions. This binding is lost following 1-methyl-4-phenylpyridinium treatment. Nur77 deficiency results in significant sensitization to dopaminergic loss following 1-methyl-4-phenylpyridinium/MPTP treatment, in vitro and in vivo. Furthermore, Nur77-deficient MPTP-treated mice displayed significantly reduced levels of dopamine and 3,4-Dihydroxyphenylacetic acid in the striatum as well as elevated post synaptic FosB activity, indicative of increased nigrostriatal damage when compared with WT MPTP-treated controls. Importantly, this sensitization in Nur77-deficient mice was rescued with ectopic Nur77 expression in the nigrostriatal system. These results indicate that the inactivation of Nur77, induced by loss of MEF2 activity, plays a critical role in nigrostriatal degeneration in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.