Mechanisms of Disease: DNA repair defects and neurological disease
Abstract
In this Review, familial and sporadic neurological disorders reported to have an etiological link with DNA repair defects are discussed, with special emphasis placed on the molecular link between the disease phenotype and the precise DNA repair defect. Of the 15 neurological disorders listed, some of which have symptoms of progeria, six--spinocerebellar ataxia with axonal neuropathy-1, Huntington's disease, Alzheimer's disease, Parkinson's disease, Down syndrome and amyotrophic lateral sclerosis--seem to result from increased oxidative stress, and the inability of the base excision repair pathway to handle the damage to DNA that this induces. Five of the conditions (xeroderma pigmentosum, Cockayne's syndrome, trichothiodystrophy, Down syndrome, and triple-A syndrome) display a defect in the nucleotide excision repair pathway, four (Huntington's disease, various spinocerebellar ataxias, Friedreich's ataxia and myotonic dystrophy types 1 and 2) exhibit an unusual expansion of repeat sequences in DNA, and four (ataxia-telangiectasia, ataxia-telangiectasia-like disorder, Nijmegen breakage syndrome and Alzheimer's disease) exhibit defects in genes involved in repairing double-strand breaks. The current overall picture indicates that oxidative stress is a major causative factor in genomic instability in the brain, and that the nature of the resulting neurological phenotype depends on the pathway through which the instability is normally repaired.
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Deficiencies in DNA repair underlie several neurological conditions in both humans and animal models.
“Deficiencies in DNA repair are known to underlie several neurological conditions in both humans and animal models [103, 147].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [147]
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- Authors
- Subba Rao, K.
- Venue
- Nature Clinical Practice Neurology
- Published
- 2007-03
- Volume
- 3
- Issue
- 3
- Pages
- 162-172
- ISSN
- 1745-834X (ISSN-L)
- 1745-8358
- OpenAlex
- W2008737416
- Cited by
- 121
- References
- 62
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 7 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 11
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Clinical Practice Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- DNA repair deficiency, neurological disorders, oxidative DNA damage, genomic instability, base excision repair, nucleotide excision repair, DNA double-strand break repair, Huntington's disease, spinocerebellar ataxia, Alzheimer's disease, Parkinson's disease, Down syndrome, amyotrophic lateral sclerosis, xeroderma pigmentosum, Cockayne syndrome, trichothiodystrophy, triple A syndrome, Friedreich's ataxia, myotonic dystrophy, ataxia telangiectasia, Nijmegen breakage syndrome, Hutchinson-Gilford progeria syndrome, repeat expansion, oxidative stress
- MeSH terms
- Animals, DNA Damage, DNA Repair, Humans, Nervous System Diseases, DNA Repair-Deficiency Disorders
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