Mechanisms of disease: DNA repair defects and neurological disease.
Nat Clin Pract Neurol
; 3(3): 162-72, 2007 Mar.
Article
em En
| MEDLINE
| ID: mdl-17342192
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Distúrbios no Reparo do DNA
/
Doenças do Sistema Nervoso
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Clin Pract Neurol
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Índia