Study May Identify Root Cause of Dementia

The brain’s inability to repair DNA to the same extent as other organs may help explain the root cause of dementia and memory loss, according to a new study.

A Nova Southeastern University-led team of investigators analyzed a type of DNA repair known as nucleotide excision repair (NER), 1 of 5 types of DNA repair used by mammalian cells, which mainly repairs damage caused by a range of cancer-causing agents such as ultraviolet (UV) and metals.
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In the study, lead author Jean Latimer, PhD, an associate professor in the department of pharmaceutical sciences at Nova Southeastern University, and colleagues evaluated mouse cell tissue cultures, using skin cells as the control to compare against other cell types. The authors, who say the results would be the same in humans, grew cells taken from various organs and compared their ability to repair DNA after exposure to ultraviolet light. According to the authors, the heart has the greatest ability to repair DNA using NER, while the brain seems to have little ability to do so.

NER is “most often associated with UV-based DNA damage, and that is how we historically understood it,” says Latimer. “The brain is not exposed to UV light, and this may be part of the reason it has so little nucleotide excision repair [ability] in the mammalian system.”

The brain, however, is also “uniquely surrounded by the blood-brain barrier, which protects it from many, but unfortunately not all, DNA-damaging chemicals circulating through our bodies,” says Latimer, noting that this blood-brain barrier “could be another reason [why] NER is low in the brain.”

Given the brain’s very limited nucleotide excision repair capacity, “we should limit our DNA-damaging exposures to the brain, i.e., X-rays or CAT scans, unless there is a compelling medical reason to use this type of radiation on the brain,” says Latimer.

Certain DNA-damaging chemicals that can cross the blood-brain barrier should be limited as well, she adds.

“We know, for example, that the nicotine in cigarettes crosses this barrier, and is in part responsible for addiction to cigarettes,” says Latimer. “But, at the same time, there are chemicals that can cause a bulky adduct to form on DNA, which is removed by NER. If not removed, this adduct causes mutation, and these misprints create pathology. The products of combustion should be limited, from any smoke, not just cigarette smoke.”

As such, chemical carcinogens from the products of combustion—smoke—should be limited, she concludes. “These can be dietary as well as inhaled, and there are also DNA-damaging chemicals present in some products. These should also be limited.”

—Mark McGraw

Reference:

1. Latimer J, Majekwana V, et al. Regulation and Disregulation of Mammalian Nucleotide Excision Repair: A Pathway to Nongermline Breast Carcinogenesis. Photochemistry and Photobiology. 2014.