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DNA-dependent protein kinase and DNA repair: relevance to Alzheimer's disease

Overview of attention for article published in Alzheimer's Research & Therapy, January 2013
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Title
DNA-dependent protein kinase and DNA repair: relevance to Alzheimer's disease
Published in
Alzheimer's Research & Therapy, January 2013
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

The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 35 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 31%
Student > Doctoral Student 4 11%
Researcher 3 9%
Student > Bachelor 3 9%
Other 2 6%
Other 3 9%
Unknown 9 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 26%
Agricultural and Biological Sciences 9 26%
Computer Science 2 6%
Neuroscience 2 6%
Medicine and Dentistry 2 6%
Other 3 9%
Unknown 8 23%