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Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration

Nucleotide balance is critically important not only in replicating cells but also in quiescent cells. This is especially true in the nervous system, where there is a high demand for adenosine triphosphate (ATP) produced from mitochondria. Mitochondria are particularly prone to oxidative stress-assoc...

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Autores principales: Fasullo, Michael, Endres, Lauren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463597/
https://www.ncbi.nlm.nih.gov/pubmed/25923076
http://dx.doi.org/10.3390/ijms16059431
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author Fasullo, Michael
Endres, Lauren
author_facet Fasullo, Michael
Endres, Lauren
author_sort Fasullo, Michael
collection PubMed
description Nucleotide balance is critically important not only in replicating cells but also in quiescent cells. This is especially true in the nervous system, where there is a high demand for adenosine triphosphate (ATP) produced from mitochondria. Mitochondria are particularly prone to oxidative stress-associated DNA damage because nucleotide imbalance can lead to mitochondrial depletion due to low replication fidelity. Failure to maintain nucleotide balance due to genetic defects can result in infantile death; however there is great variability in clinical presentation for particular diseases. This review compares genetic diseases that result from defects in specific nucleotide salvage enzymes and a signaling kinase that activates nucleotide salvage after DNA damage exposure. These diseases include Lesch-Nyhan syndrome, mitochondrial depletion syndromes, and ataxia telangiectasia. Although treatment options are available to palliate symptoms of these diseases, there is no cure. The conclusions drawn from this review include the critical role of guanine nucleotides in preventing neurodegeneration, the limitations of animals as disease models, and the need to further understand nucleotide imbalances in treatment regimens. Such knowledge will hopefully guide future studies into clinical therapies for genetic diseases.
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spelling pubmed-44635972015-06-16 Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration Fasullo, Michael Endres, Lauren Int J Mol Sci Review Nucleotide balance is critically important not only in replicating cells but also in quiescent cells. This is especially true in the nervous system, where there is a high demand for adenosine triphosphate (ATP) produced from mitochondria. Mitochondria are particularly prone to oxidative stress-associated DNA damage because nucleotide imbalance can lead to mitochondrial depletion due to low replication fidelity. Failure to maintain nucleotide balance due to genetic defects can result in infantile death; however there is great variability in clinical presentation for particular diseases. This review compares genetic diseases that result from defects in specific nucleotide salvage enzymes and a signaling kinase that activates nucleotide salvage after DNA damage exposure. These diseases include Lesch-Nyhan syndrome, mitochondrial depletion syndromes, and ataxia telangiectasia. Although treatment options are available to palliate symptoms of these diseases, there is no cure. The conclusions drawn from this review include the critical role of guanine nucleotides in preventing neurodegeneration, the limitations of animals as disease models, and the need to further understand nucleotide imbalances in treatment regimens. Such knowledge will hopefully guide future studies into clinical therapies for genetic diseases. MDPI 2015-04-27 /pmc/articles/PMC4463597/ /pubmed/25923076 http://dx.doi.org/10.3390/ijms16059431 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Fasullo, Michael
Endres, Lauren
Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration
title Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration
title_full Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration
title_fullStr Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration
title_full_unstemmed Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration
title_short Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration
title_sort nucleotide salvage deficiencies, dna damage and neurodegeneration
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463597/
https://www.ncbi.nlm.nih.gov/pubmed/25923076
http://dx.doi.org/10.3390/ijms16059431
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