Research Paper on New Viewpoints on Pro-Oxidant Metal Inhibition of Oxidized Genome Damage and Repair in Neurological Diseases

Description

Title: New Viewpoints on Pro-Oxidant Metal Inhibition of Oxidized Genome Damage and Repair in Neurological Diseases

Abstract: Most neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, still lack a clear primary cause or causes for neuronal death. However, it has been repeatedly noted that certain etiological factors, such as oxidative stress, protein misfolding/aggregation, redox metal accumulation, and different kinds of genome damage, are linked to pathological changes in the affected brain region(s). Despite the recent focus on redox metal toxicity, its potential as a therapeutic target is still in doubt, largely due to the lack of a mechanistic understanding of the metal dyshomeostasis in affected neurons. Additionally, it has been demonstrated in earlier studies that metals play a role in genome damage, both directly and through the production of reactive oxygen species (ROS), but little is known about their effect on genome repair. Our recent research has shown that excessive levels of iron and copper found in brain neurons from patients with neurodegenerative diseases can not only cause genome damage but also interfere with the repair process by oxidatively inhibiting NEIL DNA glycosylases, which start the repairing of oxidized DNA bases. A combination of metal chelators and reducing agents was able to reverse the inhibitory effect, which emphasizes the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop efficient therapeutic strategies. In this review, we have concentrated on the pro-oxidant metal toxicity repair pathway as a potential target for lowering neurological disease pro-oxidant metal toxicity.

Keywords: redox transition metals; heavy metals; DNA base excision repair; metal toxicity; metal homeostasis; neurodegeneration; Alzheimer’s disease; Parkinson’s disease

Paper Quality: SCOPUS / Web of Science Level Research Paper

Subject: Biomolecules

Writer Experience: 20+ Years

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