High iron, copper levels block brain-cell DNA repair

May 20, 2011, University of Texas Medical Branch at Galveston

No one knows the cause of most cases of Alzheimer's, Parkinson's and other neurodegenerative disorders. But researchers have found that certain factors are consistently associated with these debilitating conditions. One is DNA damage by reactive oxygen species, highly destructive molecules usually formed as a byproduct of cellular respiration. Another is the presence of excessive levels of copper and iron in regions of the brain associated with the particular disorder.

University of Texas Medical Branch at Galveston researchers have discovered how these two pieces of the neurodegenerative disease puzzle fit together, a connection they describe in a review article in the current Journal of Alzheimer's Disease. A high level of copper or iron, they say, can function as a "double whammy" in the brain by both helping generate large numbers of the DNA-attacking reactive oxygen species and interfering with the machinery of that prevents the deleterious consequences of genome damage.

"It's been suggested that an imbalance of DNA damage and repair produces a buildup of unrepaired that can initiate neurodegenerative pathology," said postdoctoral fellow Muralidhar Hegde, lead author of the paper. "We don't yet know enough about all the involved, but we have found multiple toxic mechanisms linking elevated iron and copper levels in the brain and extensive DNA damage — pathological features associated with most neurodegenerative disorders."

Humans ordinarily have small amounts of iron and copper in their bodies — in fact, the elements are essential to health. But some people's tissues contain much larger quantities of iron or copper, which overwhelm the proteins that normally bind the metals and sequester them for safe storage. The result: so-called "free" iron or copper ions, circulating in the blood and able to initiate chemical reactions that produce reactive oxygen species.

"Reactive cause the majority of the brain cell DNA damage that we see in Alzheimer's and Parkinson's disease, as well as most other neurodegenerative disorders," Hegde said. "It's bad enough if this damage occurs on one strand of the DNA double helix, but if both strands are damaged at locations close to each other you could have a double-strand break, which would be fatal to the cell."

Normally, special DNA repair enzymes would quickly mend the injury, restoring the genome's integrity. But experiments conducted by Hegde and his colleagues showed that iron and copper significantly interfere with the activity of two DNA repair enzymes, known as NEIL1 and NEIL2.

"Our results show that by inhibiting NEIL1 and NEIL2, iron and copper play an important role in the accumulation of in neurodegenerative diseases," Hegde said.

The researchers got a surprise when they tested substances that bond to iron and copper and could protect NEIL1 from the metals. One of the strongest protective agents was the common South Asian spice curcumin, which also has been shown to have other beneficial health effects.

"The results from curcumin were quite beautiful, actually," Hegde said. "It was very effective in maintaining NEIL activity in cells exposed to both and iron."

Related Stories

Recommended for you

A new theory on reducing cardiovascular disease risk in binge drinkers

January 23, 2018
A new study shows that binge drinkers have increased levels of a biomarker molecule—microRNA-21—that may contribute to poor vascular function.

Flu infection study increases understanding of natural immunity

January 23, 2018
People with higher levels of antibodies against the stem portion of the influenza virus hemagglutinin (HA) protein have less viral shedding when they get the flu, but do not have fewer or less severe signs of illness, according ...

Onions could hold key to fighting antibiotic resistance

January 22, 2018
A type of onion could help the fight against antibiotic resistance in cases of tuberculosis, a UCL and Birkbeck-led study suggests.

New long-acting approach for malaria therapy developed

January 22, 2018
A new study, published in Nature Communications, conducted by the University of Liverpool and the Johns Hopkins University School of Medicine highlights a new 'long acting' medicine for the prevention of malaria.

Virus shown to be likely cause of mystery polio-like illness

January 22, 2018
A major review by UNSW researchers has identified strong evidence that a virus called Enterovirus D68 is the cause of a mystery polio-like illness that has paralysed children in the US, Canada and Europe.

Creation of synthetic horsepox virus could lead to more effective smallpox vaccine

January 19, 2018
UAlberta researchers created a new synthetic virus that could lead to the development of a more effective vaccine against smallpox. The discovery demonstrates how techniques based on the use of synthetic DNA can be used to ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.