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Current Aging Science
ISSN (Print): 1874-6098
ISSN (Online): 1874-6128
VOLUME: 3
ISSUE: 1
DOI: 10.2174/1874609811003010003









DNA Repair in Premature Aging Disorders and Neurodegeneration

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Author(s): Fabio Coppede and Lucia Migliore
Pages 3-19 (17)
Abstract:
The accumulation of DNA damage has been widely implicated in premature aging and neurodegeneration. Progeroid syndromes with defects in the cellular response to DNA damage suggest that progressive genome instability represents an important aspect of the aging process. Moreover, most of the major neurodegenerative diseases are characterized by the accumulation of neuronal DNA damage, suggesting that impaired DNA repair mechanisms might be relevant to both premature aging and neurodegeneration. Two progeroid syndromes, Hutchinson-Gilford progeria syndrome and Werners syndrome, are characterized by clinical features mimicking physiological aging at an early age and molecular studies have implicated decreased cell proliferation and altered DNA-damage responses as common causal mechanisms in the pathogenesis of both diseases. Defects in nucleotide excision repair cause three distinct human diseases: xeroderma pigmentosum, Cockaynes syndrome and trichothiodystrophy; each of them is characterized by premature onset of pathologies that overlap with those associated with old age in humans. Increasing evidence also suggests that an impaired DNA repair, particularly the base excision repair pathway, might play a fundamental role in the development of age-related neurodegenerative diseases such as Alzheimers disease, Parkinsons disease, amyotrophic lateral sclerosis and Huntington s disease. Here, we review the current knowledge on the role of DNA repair in premature aging and neurodegenerative diseases.
Keywords:
DNA repair, premature aging, neurodegenerative diseases, Hutchinson-Gilford progeria syndrome (HGPS), Werner's syndrome (WS), xeroderma pigmentosum (XP), Cockayne's syndrome (CS), trichothiodystrophy (TTD), Alzheimer's disease (AD), Parkinson's disease (PD)
Affiliation:
Department of Neuroscience, University of Pisa, Via Roma 67, 56126, Pisa, Italy.