New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases
The 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...
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| Format: | article |
| Language: | English |
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2014
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| Online Access: | http://repositorio-indicasat.org.pa/handle/123456789/18 |
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| _version_ | 1869652476337061888 |
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| author | Mitra, Joy |
| author2 | Guerrero, Erika N. Hegde, Pavana M. Wang, Haibo Boldogh, Istvan Sharaf Rao, Kosagi Mitra, Sankar Hegde, Muralidhar L. |
| author2_role | author author author author author author author |
| author_browse | Boldogh, Istvan Guerrero, Erika N. Hegde, Muralidhar L. Hegde, Pavana M. Mitra, Joy Mitra, Sankar Sharaf Rao, Kosagi Wang, Haibo |
| author_facet | Mitra, Joy Guerrero, Erika N. Hegde, Pavana M. Wang, Haibo Boldogh, Istvan Sharaf Rao, Kosagi Mitra, Sankar Hegde, Muralidhar L. |
| author_role | author |
| collection | Repositorio INDICASAT |
| dc.creator.none.fl_str_mv | Mitra, Joy Guerrero, Erika N. Hegde, Pavana M. Wang, Haibo Boldogh, Istvan Sharaf Rao, Kosagi Mitra, Sankar Hegde, Muralidhar L. |
| dc.date.none.fl_str_mv | 2014-07-17 2020-02-10T15:46:32Z 2020-02-10T15:46:32Z |
| dc.format.none.fl_str_mv | application/pdf application/pdf |
| dc.identifier.none.fl_str_mv | http://repositorio-indicasat.org.pa/handle/123456789/18 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | biomolecules |
| dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.source.none.fl_str_mv | reponame:Repositorio INDICASAT instname:Instituto de Investigaciones Científicas y Servicios de Alta Tecnología instacron:INDICASAT |
| dc.subject.none.fl_str_mv | Parkinson’s disease Alzheimer’s disease neurodegeneration metal homeostasis metal toxicity DNA base excision repair heavy metals redox transition metals |
| dc.title.none.fl_str_mv | New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases |
| dc.type.none.fl_str_mv | info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| description | The 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. |
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| oai_identifier_str | oai:repositorio-indicasat.org.pa:123456789/18 |
| publishDate | 2014 |
| publishDateSort | 2014 |
| publisher.none.fl_str_mv | biomolecules |
| reponame_str | Repositorio INDICASAT |
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| spelling | New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological DiseasesMitra, JoyGuerrero, Erika N.Hegde, Pavana M.Wang, HaiboBoldogh, IstvanSharaf Rao, KosagiMitra, SankarHegde, Muralidhar L.Parkinson’s diseaseAlzheimer’s diseaseneurodegenerationmetal homeostasismetal toxicityDNA base excision repairheavy metalsredox transition metalsThe 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.The 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.biomolecules2020-02-10T15:46:32Z2020-02-10T15:46:32Z2014-07-17info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://repositorio-indicasat.org.pa/handle/123456789/18enginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/4.0/reponame:Repositorio INDICASATinstname:Instituto de Investigaciones Científicas y Servicios de Alta Tecnologíainstacron:INDICASAT2020-05-27T10:06:39Zmail@mail.com - |
| spellingShingle | New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases Mitra, Joy Parkinson’s disease Alzheimer’s disease neurodegeneration metal homeostasis metal toxicity DNA base excision repair heavy metals redox transition metals |
| status_str | publishedVersion |
| title | New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases |
| title_full | New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases |
| title_fullStr | New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases |
| title_full_unstemmed | New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases |
| title_short | New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases |
| title_sort | New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases |
| topic | Parkinson’s disease Alzheimer’s disease neurodegeneration metal homeostasis metal toxicity DNA base excision repair heavy metals redox transition metals |
| url | http://repositorio-indicasat.org.pa/handle/123456789/18 |