ArticleThe Journal of biological chemistry2011
Enhanced autophagy from chronic toxicity of iron and mutant A53T α-synuclein: implications for neuronal cell death in Parkinson disease.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 84 citations in OpenAlex.
- Microplastics and neurotoxicity: could prenatal exposure to microplastics boost congenital enteric neuropathies?Frontiers in toxicology · 2026Review
- Use of Cosmetics in Pregnancy and Neurotoxicity: Can It Increase the Risk of Congenital Enteric Neuropathies?Biomolecules · 2024Review
- In vitro reconstitution of transition metal transporters.The Journal of biological chemistry · 2024Review
- Iron-inhibited autophagy via transcription factor ZFP27 in Parkinson's disease.Journal of cellular and molecular medicine · 2023Article
- Midbrain dopamine oxidation links ubiquitination of glutathione peroxidase 4 to ferroptosis of dopaminergic neurons.The Journal of clinical investigation · 2023Article
- Review
- The Associations between Metalloestrogens, GSTP1, and SLC11A2 Polymorphism and the Risk of Endometrial Cancer.Nutrients · 2022Article
- Toxic Feedback Loop Involving Iron, Reactive Oxygen Species, α-Synuclein and Neuromelanin in Parkinson's Disease and Intervention with Turmeric.Molecular neurobiology · 2021Review
- Iron Overload Induces Apoptosis and Cytoprotective Autophagy Regulated by ROS Generation in Mc3t3-E1 Cells.Biological trace element research · 2021Article
- Oxidative Stress in Parkinson's Disease: Potential Benefits of Antioxidant Supplementation.Oxidative medicine and cellular longevity · 2020Review
- Nicotinamide-N-methyltransferase controls behavior, neurodegeneration and lifespan by regulating neuronal autophagy.PLoS genetics · 2018Article
- Intercellular transfer of pathogenic α-synuclein by extracellular vesicles is induced by the lipid peroxidation product 4-hydroxynonenal.Neurobiology of aging · 2018Article
- Expression of Iron Transporters and Pathological Hallmarks of Parkinson's and Alzheimer's Diseases in the Brain of Young, Adult, and Aged Rats.Molecular neurobiology · 2017Article
- Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.Brain research bulletin · 2017Review
- Saturated hydrogen saline ameliorates lipopolysaccharide-induced acute lung injury by reducing excessive autophagy.Experimental and therapeutic medicine · 2017Article
- The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders.International journal of molecular sciences · 2017Review
- The Central Role of Biometals Maintains Oxidative Balance in the Context of Metabolic and Neurodegenerative Disorders.Oxidative medicine and cellular longevity · 2017Review
- Metal Dyshomeostasis and Their Pathological Role in Prion and Prion-Like Diseases: The Basis for a Nutritional Approach.Frontiers in neuroscience · 2017Review
- Regulation of DMT1 on autophagy and apoptosis in osteoblast.International journal of medical sciences · 2017Article
- Parkinson's Disease Skin Fibroblasts Display Signature Alterations in Growth, Redox Homeostasis, Mitochondrial Function, and Autophagy.Frontiers in neuroscience · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Parkinson disease (PD), a prevalent neurodegenerative motor disorder, is characterized by the rather selective loss of dopaminergic neurons and the presence of α-synuclein-enriched Lewy body inclusions in the substantia nigra of the midbrain. Although the etiology of PD remains incompletely understood, emerging evidence suggests that dysregulated iron homeostasis may be involved. Notably, nigral dopaminergic neurons are enriched in iron, the uptake of which is facilitated by the divalent metal ion transporter DMT1. To clarify the role of iron in PD, we generated SH-SY5Y cells stably expressing DMT1 either singly or in combination with wild type or mutant α-synuclein. We found that DMT1 overexpression dramatically enhances Fe(2+) uptake, which concomitantly promotes cell death. This Fe(2+)-mediated toxicity is aggravated by the presence of mutant α-synuclein expression, resulting in increased oxidative stress and DNA damage. Curiously, Fe(2+)-mediated cell death does not appear to involve apoptosis. Instead, the phenomenon seems to occur as a result of excessive autophagic activity. Accordingly, pharmacological inhibition of autophagy reverses cell death mediated by Fe(2+) overloading. Taken together, our results suggest a role for iron in PD pathogenesis and provide a mechanism underlying Fe(2+)-mediated cell death.
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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.