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dc.contributor.authorMitra, Joy
dc.contributor.authorGuerrero, Erika N
dc.contributor.authorHegde, Pavana M
dc.contributor.authorWang, Haibo
dc.contributor.authorBoldogh, Istvan
dc.contributor.authorRao, Kosagi Sharaf
dc.contributor.authorMitra, Sankar
dc.contributor.authorHegde, Muralidhar L
dc.date.accessioned2020-08-19T23:18:13Z
dc.date.available2020-08-19T23:18:13Z
dc.date.issued2014-07-17
dc.identifier.otherhttps://doi.org/10.3390/biom4030678
dc.identifier.urihttp://repositorio-indicasat.org.pa/handle/123456789/244
dc.descriptionThe primary cause(s) of neuronal death in most cases of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are still unknown. However, the association of certain etiological factors, e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to the genome, to pathological changes in the affected brain region(s) have been consistently observed. While redox metal toxicity received major attention in the last decade, its potential as a therapeutic target is still at a cross-roads, mostly because of the lack of mechanistic understanding of metal dyshomeostasis in affected neurons. Furthermore, previous studies have established the role of metals in causing genome damage, both directly and via the generation of reactive oxygen species (ROS), but little was known about their impact on genome repair. Our recent studies demonstrated that excess levels of iron and copper observed in neurodegenerative disease-affected brain neurons could not only induce genome damage in neurons, but also affect their repair by oxidatively inhibiting NEIL DNA glycosylases, which initiate the repair of oxidized DNA bases. The inhibitory effect was reversed by a combination of metal chelators and reducing agents, which underscore the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop effective therapeutic approaches. In this review, we have focused on the oxidative genome damage repair pathway as a potential target for reducing pro-oxidant metal toxicity in neurological diseases.en_US
dc.description.abstractThe primary cause(s) of neuronal death in most cases of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are still unknown. However, the association of certain etiological factors, e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to the genome, to pathological changes in the affected brain region(s) have been consistently observed. While redox metal toxicity received major attention in the last decade, its potential as a therapeutic target is still at a cross-roads, mostly because of the lack of mechanistic understanding of metal dyshomeostasis in affected neurons. Furthermore, previous studies have established the role of metals in causing genome damage, both directly and via the generation of reactive oxygen species (ROS), but little was known about their impact on genome repair. Our recent studies demonstrated that excess levels of iron and copper observed in neurodegenerative disease-affected brain neurons could not only induce genome damage in neurons, but also affect their repair by oxidatively inhibiting NEIL DNA glycosylases, which initiate the repair of oxidized DNA bases. The inhibitory effect was reversed by a combination of metal chelators and reducing agents, which underscore the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop effective therapeutic approaches. In this review, we have focused on the oxidative genome damage repair pathway as a potential target for reducing pro-oxidant metal toxicity in neurological diseases.en_US
dc.language.isoengen_US
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectredox transition metalsen_US
dc.subjectheavy metalsen_US
dc.subjectDNA base excision repairen_US
dc.subjectmetal toxicityen_US
dc.subjectmetal homeostasisen_US
dc.subjectneurodegenerationen_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectParkinson’s diseaseen_US
dc.titleNew Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseasesen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dc.typeinfo:edu-repo/semantics/publishedVersion


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