ArticleThe Journal of biological chemistry2010
Specific Inhibition of NEIL-initiated repair of oxidized base damage in human genome by copper and iron: potential etiological linkage to neurodegenerative diseases.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Neuroprotective properties of curcumin in toxin-base animal models of Parkinson's disease: a systematic experiment literatures review.BMC complementary and alternative medicine · 2017Pooled it
- Facilitated DNA damage repair as an emerging therapeutic strategy for inflammatory and fibrotic diseases.RSC chemical biology · 2026Review
- Longitudinal assessment of DNA repair signature trajectory in prodromal versus established Parkinson's disease.NPJ Parkinson's disease · 2025Article
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- The Effects of Fisetin and Curcumin on Oxidative Damage Caused by Transition Metals in Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair.Biomedicines · 2024Review
- Dysfunctional copper homeostasis inRedox biochemistry and chemistry · 2024Article
- Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its Activity.Antioxidants (Basel, Switzerland) · 2023Article
- SARS-CoV-2 and the central nervous system: Emerging insights into hemorrhage-associated neurological consequences and therapeutic considerations.Ageing research reviews · 2022Review
- DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders.International journal of molecular sciences · 2022Review
- UV Protection in the Cornea: Failure and Rescue.Biology · 2022Review
- Impact of Oxidative DNA Damage and the Role of DNA Glycosylases in Neurological Dysfunction.International journal of molecular sciences · 2021Review
- Quercetin attenuates neurotoxicity induced by iron oxide nanoparticles.Journal of nanobiotechnology · 2021Review
- "Metal elements and pesticides as risk factors for Parkinson's disease - A review".Toxicology reports · 2021Review
- Pervasive Genomic Damage in Experimental Intracerebral Hemorrhage: Therapeutic Potential of a Mechanistic-Based Carbon Nanoparticle.ACS nano · 2020Article
- Potential therapeutic effects of antagonizing adenosine AMolecular and cellular biochemistry · 2020Article
- Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Protective Effects of Curcumin Against Ischemia-Reperfusion Injury in the Nervous System.Molecular neurobiology · 2019Review
- Colocalization of Aluminum and Iron in Nuclei of Nerve Cells in Brains of Patients with Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2018Article
- Chronic oxidative damage together with genome repair deficiency in the neurons is a double whammy for neurodegeneration: Is damage response signaling a potential therapeutic target?Mechanisms of ageing and development · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Dyshomeostasis of transition metals iron and copper as well as accumulation of oxidative DNA damage have been implicated in multitude of human neurodegenerative diseases, including Alzheimer disease and Parkinson disease. These metals oxidize DNA bases by generating reactive oxygen species. Most oxidized bases in mammalian genomes are repaired via the base excision repair pathway, initiated with one of four major DNA glycosylases: NTH1 or OGG1 (of the Nth family) or NEIL1 or NEIL2 (of the Nei family). Here we show that Fe(II/III) and Cu(II) at physiological levels bind to NEIL1 and NEIL2 to alter their secondary structure and strongly inhibit repair of mutagenic 5-hydroxyuracil, a common cytosine oxidation product, both in vitro and in neuroblastoma (SH-SY5Y) cell extract by affecting the base excision and AP lyase activities of NEILs. The specificity of iron/copper inhibition of NEILs is indicated by a lack of similar inhibition of OGG1, which also indicated that the inhibition is due to metal binding to the enzymes and not DNA. Fluorescence and surface plasmon resonance studies show submicromolar binding of copper/iron to NEILs but not OGG1. Furthermore, Fe(II) inhibits the interaction of NEIL1 with downstream base excision repair proteins DNA polymerase beta and flap endonuclease-1 by 4-6-fold. These results indicate that iron/copper overload in the neurodegenerative diseases could act as a double-edged sword by both increasing oxidative genome damage and preventing their repair. Interestingly, specific chelators, including the natural chemopreventive compound curcumin, reverse the inhibition of NEILs both in vitro and in cells, suggesting their therapeutic potential.
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