DNA repair deficiency in neuropathogenesis: when all roads lead to mitochondria
Abstract Mutations in DNA repair enzymes can cause two neurological clinical manifestations: a developmental impairment and a degenerative disease. Polynucleotide kinase 3′-phosphatase (PNKP) is an enzyme that is actively involved in DNA repair in both single and double strand break repair systems....
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Translational Neurodegeneration |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40035-019-0156-x |
| _version_ | 1830510557648650240 |
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| author | Luis Bermúdez-Guzmán Alejandro Leal |
| author_facet | Luis Bermúdez-Guzmán Alejandro Leal |
| author_sort | Luis Bermúdez-Guzmán |
| collection | DOAJ |
| description | Abstract Mutations in DNA repair enzymes can cause two neurological clinical manifestations: a developmental impairment and a degenerative disease. Polynucleotide kinase 3′-phosphatase (PNKP) is an enzyme that is actively involved in DNA repair in both single and double strand break repair systems. Mutations in this protein or others in the same pathway are responsible for a complex group of diseases with a broad clinical spectrum. Besides, mitochondrial dysfunction also has been consolidated as a hallmark of brain degeneration. Here we provide evidence that supports a shared role between mitochondrial dysfunction and DNA repair defects in the pathogenesis of the nervous system. As models, we analyze PNKP-related disorders, focusing on Charcot-Marie-Tooth disease and ataxia. A better understanding of the molecular dynamics of this relationship could provide improved diagnosis and treatment for neurological diseases. |
| first_indexed | 2024-12-22T01:54:25Z |
| format | Article |
| id | doaj.art-500023f8d09a4d308bb1c8b6056164fb |
| institution | Directory Open Access Journal |
| issn | 2047-9158 |
| language | English |
| last_indexed | 2024-12-22T01:54:25Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj.art-500023f8d09a4d308bb1c8b6056164fb2022-12-21T18:42:49ZengBMCTranslational Neurodegeneration2047-91582019-05-018111410.1186/s40035-019-0156-xDNA repair deficiency in neuropathogenesis: when all roads lead to mitochondriaLuis Bermúdez-Guzmán0Alejandro Leal1Section of Genetics and Biotechnology, School of Biology, Universidad de Costa RicaSection of Genetics and Biotechnology, School of Biology, Universidad de Costa RicaAbstract Mutations in DNA repair enzymes can cause two neurological clinical manifestations: a developmental impairment and a degenerative disease. Polynucleotide kinase 3′-phosphatase (PNKP) is an enzyme that is actively involved in DNA repair in both single and double strand break repair systems. Mutations in this protein or others in the same pathway are responsible for a complex group of diseases with a broad clinical spectrum. Besides, mitochondrial dysfunction also has been consolidated as a hallmark of brain degeneration. Here we provide evidence that supports a shared role between mitochondrial dysfunction and DNA repair defects in the pathogenesis of the nervous system. As models, we analyze PNKP-related disorders, focusing on Charcot-Marie-Tooth disease and ataxia. A better understanding of the molecular dynamics of this relationship could provide improved diagnosis and treatment for neurological diseases.http://link.springer.com/article/10.1186/s40035-019-0156-xDNA repairMitochondrial dysfunctionNeurodegenerationAtaxiaPNKP |
| spellingShingle | Luis Bermúdez-Guzmán Alejandro Leal DNA repair deficiency in neuropathogenesis: when all roads lead to mitochondria Translational Neurodegeneration DNA repair Mitochondrial dysfunction Neurodegeneration Ataxia PNKP |
| title | DNA repair deficiency in neuropathogenesis: when all roads lead to mitochondria |
| title_full | DNA repair deficiency in neuropathogenesis: when all roads lead to mitochondria |
| title_fullStr | DNA repair deficiency in neuropathogenesis: when all roads lead to mitochondria |
| title_full_unstemmed | DNA repair deficiency in neuropathogenesis: when all roads lead to mitochondria |
| title_short | DNA repair deficiency in neuropathogenesis: when all roads lead to mitochondria |
| title_sort | dna repair deficiency in neuropathogenesis when all roads lead to mitochondria |
| topic | DNA repair Mitochondrial dysfunction Neurodegeneration Ataxia PNKP |
| url | http://link.springer.com/article/10.1186/s40035-019-0156-x |
| work_keys_str_mv | AT luisbermudezguzman dnarepairdeficiencyinneuropathogenesiswhenallroadsleadtomitochondria AT alejandroleal dnarepairdeficiencyinneuropathogenesiswhenallroadsleadtomitochondria |