ArticleAntioxidants & redox signaling2014
Oxidation of survival factor MEF2D in neuronal death and Parkinson's disease.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Targeting chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapeutic potential.Acta pharmacologica Sinica · 2025Review
- Article
- The Molecular and Biological Function of MEF2D in Leukemia.Advances in experimental medicine and biology · 2024Review
- Deficient chaperone-mediated autophagy facilitates LPS-induced microglial activation via regulation of the p300/NF-κB/NLRP3 pathway.Science advances · 2023Article
- Chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapy.Molecular and cellular biochemistry · 2023Review
- The Role of MEF2 Transcription Factor Family in Neuronal Survival and Degeneration.International journal of molecular sciences · 2023Review
- Chaperone-mediated autophagy protects cardiomyocytes against hypoxic-cell death.American journal of physiology. Cell physiology · 2022Article
- Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy.Journal of translational medicine · 2022Article
- Chaperone-mediated autophagy degrades Keap1 and promotes Nrf2-mediated antioxidative response.Aging cell · 2022Article
- A focus on natural products for preventing and cure of mitochondrial dysfunction in Parkinson's disease.Metabolic brain disease · 2022Review
- Review
- Chaperone-mediated autophagy and disease: Implications for cancer and neurodegeneration.Molecular aspects of medicine · 2021Article
- Chaperone-mediated autophagy controls the turnover of E3 ubiquitin ligase MARCHF5 and regulates mitochondrial dynamics.Autophagy · 2021Article
- HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug Addiction.Biology · 2021Article
- Expression levels of specific microRNAs are increased after exercise and are associated with cognitive improvement in Parkinson's disease.Molecular medicine reports · 2021Article
- Isoflurane post-conditioning contributes to anti-apoptotic effect after cerebral ischaemia in rats through the ERK5/MEF2D signaling pathway.Journal of cellular and molecular medicine · 2021Article
- Parkinson's Disease Master Regulators on Substantia Nigra and Frontal Cortex and Their Use for Drug Repositioning.Molecular neurobiology · 2021Article
- Article
- Regulation of IFN-Is by MEF2D Promotes Inflammatory Homeostasis in Microglia.Journal of inflammation research · 2021Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsDysfunction of myocyte enhancer factor 2D (MEF2D), a key survival protein and transcription factor, underlies the pathogenic loss of dopaminergic (DA) neurons in Parkinson's disease (PD). Both genetic factors and neurotoxins associated with PD impair MEF2D function in vitro and in animal models of PD. We investigated whether distinct stress conditions target MEF2D via converging mechanisms.
resultsWe showed that exposure of a DA neuronal cell line to 6-hyroxydopamine (6-OHDA), which causes PD in animals models, led to direct oxidative modifications of MEF2D. Oxidized MEF2D bound to heat-shock cognate protein 70 kDa, the key regulator for chaperone-mediated autophagy (CMA), at a higher affinity. Oxidative stress also increased the level of lysosomal-associated membrane protein 2A (LAMP2A), the rate-limiting receptor for CMA substrate flux, and stimulated CMA activity. These changes resulted in accelerated degradation of MEF2D. Importantly, 6-OHDA induced MEF2D oxidation and increased LAMP2A in the substantia nigra pars compacta region of the mouse brain. Consistently, the levels of oxidized MEF2D were much higher in postmortem PD brains compared with the controls. Functionally, reducing the levels of either MEF2D or LAMP2A exacerbated 6-OHDA-induced death of the DA neuronal cell line. Expression of an MEF2D mutant that is resistant to oxidative modification protected cells from 6-OHDA-induced death. INNOVATION: This study showed that oxidization of survival protein MEF2D is one of the pathogenic mechanisms involved in oxidative stress-induced DA neuronal death.
conclusionOxidation of survival factor MEF2D inhibits its function, underlies oxidative stress-induced neurotoxicity, and may be a part of the PD pathogenic process.
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