期刊
NEUROTHERAPEUTICS
卷 10, 期 4, 页码 817-830出版社
SPRINGER
DOI: 10.1007/s13311-013-0210-9
关键词
Neurodegeneration; DNA damage; DNA repair; Chromatin modification; Epigenetics
资金
- National Institutes of Health [NS071056]
- New York State Spinal Cord Injury Research Program [CO19772]
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Burke Medical Research Foundation
The integrity of the genome is continuously challenged by both endogenous and exogenous DNA damaging agents. Neurons, due to their post-mitotic state, high metabolism, and longevity are particularly prone to the accumulation of DNA lesions. Indeed, DNA damage has been suggested as a major contributor to both age-associated neurodegenerative diseases and acute neurological injury. The DNA damage response is a key factor in maintaining genome integrity. It relies on highly dynamic posttranslational modifications of the chromatin and DNA repair proteins to allow signaling, access, and repair of the lesion. Drugs that modulate the activity of the enzymes responsible for these modifications have emerged as attractive therapeutic compounds to treat neurodegeneration. In this review, we discuss the role of DNA double-strand breaks and abnormal chromatin modification patterns in a range of neurodegenerative conditions, and the chromatin modifiers that might ameliorate them. Finally, we suggest that understanding the epigenetic modifications specific to neuronal DNA repair is crucial for the development of efficient neurotherapeutic strategies.
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