Title |
DNA-dependent protein kinase and DNA repair: relevance to Alzheimer's disease
|
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Published in |
Alzheimer's Research & Therapy, April 2013
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DOI | 10.1186/alzrt167 |
Pubmed ID | |
Authors |
Jyotshna Kanungo |
Abstract |
The pathological hallmark of Alzheimer's disease (AD), the leading cause of senile dementia, involves region-specific neuronal death and an accumulation of neuronal and extracellular lesions termed neurofibrillary tangles and senile plaques, respectively. One of the biochemical abnormalities observed in AD is reduced DNA end-joining activity. The reduced capacity of post-mitotic neurons for some types of DNA repair is further compromised by aging. The predominant mechanism to repair double-strand DNA (dsDNA) breaks (DSB) is non-homologous end joining (NHEJ), which requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK is a holoenzyme comprising the p460 kDa DNA-PK catalytic subunit (DNA-PKcs) and the Ku heterodimer consisting of p86 (Ku 80) and p70 (Ku 70) subunits. Ku binds to DNA ends first and then recruits DNA-PKcs during NHEJ. However, in AD brains, reduced NHEJ activity has been reported along with reduced levels of DNA-PKcs and the Ku proteins, indicating a potential link between AD and dsDNA damage. Since age-matched control brains also show a reduction in these protein levels, whether there is a direct link between NHEJ ability and AD remains unknown. Possible mechanisms involving the role of DNA-PK in neurodegeneration, a benchmark of AD, are the focus of this review. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 39 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 11 | 28% |
Student > Doctoral Student | 4 | 10% |
Researcher | 4 | 10% |
Student > Bachelor | 3 | 8% |
Other | 2 | 5% |
Other | 3 | 8% |
Unknown | 12 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 9 | 23% |
Biochemistry, Genetics and Molecular Biology | 8 | 21% |
Computer Science | 3 | 8% |
Medicine and Dentistry | 3 | 8% |
Neuroscience | 2 | 5% |
Other | 4 | 10% |
Unknown | 10 | 26% |