Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration
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Authors
Fasullo, Michael
Endres, Laurel
Issue Date
2015
Type
Article
Language
en_US
Keywords
nucleotide balance , replicating cells , quiescent cells , adenosine triphosphate , mitochondria , oxidative stress , mitochondrial depletion , replication fidelity , nucleotide salvage enzymes , signaling kinase , DNA damage , Lesch-Nyhan syndrome , mitochondrial depletion syndrome , ataxia telangiectasia , guanine nucleotides , neurodegeneration
Alternative Title
International Journal of Molecular Sciences
Abstract
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.
Description
Citation
Fasullo, M., & Endres, L. (2015). Nucleotide salvage deficiencies, DNA damage and neurodegeneration. International Journal of Molecular Sciences, 16, 9431-9449. doi:10.3390/ijms16059431
Publisher
International Journal of Molecular Sciences
License
Journal
Volume
Issue
PubMed ID
DOI
ISSN
1422-0067