Taking Iron Out to Cure Age-Related Diseases

Chemists from Duke University have combined their knowledge and skills in developing methods for uniting the iron content of the brain to fight the neurological destruction caused by Parkinson’s and Alzheimer’s diseases. The solution derived was to take out potentially damaging forms of iron, that produce dangerous free radicals, while leaving beneficial forms of iron alone to conduct vital operations in the body.

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Going back to the article, Katherine Franz, who is an assistant chemistry professor at Duke, remarked that using existing chelating or metal-binding molecules to attack iron in the brain can be tricky since iron is indispensable to the body. However, the chemists aim to only go after and take out the iron, that is causing harm, and not the iron found on healthy sites.

During the national meeting of the American Chemical Society held in Boston last August 23, 2007, Franz discussed the said studies at Duke with graduate student, Louise Charkoudian, in order to come up with a formula to devise sensitive chemical sentinels they would call pro-chelators. The pro-chelators will serve as metal-binding agents that are wrapped in chemical cages. As such, pro-chelators can enter the brain and wait in reserve until they meet a potential location of damage.

Such potential damaged site has both iron and the molecule hydrogen peroxide. When iron and hydrogen peroxide react with each other, this is called Fenton reaction. Such Fenton reaction can lead to the production of a highly reactive and toxic oxygen-containing chemical group called a hydroxyl radical. These toxic hydroxyl radicals can cause oxidative stress in cells of brain that have been associated with Parkinson’s, Alzheimer’s, and other age-related diseases like macular degeneration in the eyes.

In order to deflect the damage caused by these toxic chemicals, the pro-chelators, which contain phenols, work by wearing chemical masks around themselves that would keep them from binding with beneficial forms of iron or other metals like those found in some essential enzymes. Since the presence hydrogen peroxide in excessive amounts will trigger the unmasking of the pro-chelators, such condition would then allow the phenols to pacify and inactivate the harmful iron.

The initial work of Franz and Charkoudian was published in the Journal of the American Chemical Society last Sept. 27, 2006. Such journal reported their first formula for the said pro-chelator. Their study was supported by the Parkinson’s Disease Foundation and Duke University. This year, Franz stated that they will work on a second generation of pro-chelator compounds. This new formulation hopes to be better than the one reported last year in such a way that the second generation will be more sensitive and better respond to the chemical environment of the brain. Such new generation is set to be published on Dalton Transactions journal.

Franz and Charkoudian’s initial study have been done in laboratory glassware. For this second generation, the pair has now begun working with living cells. Franz has reported the current experiment looks promising. They have observed that iron only binds when the levels of hydrogen peroxide are increased. This condition would normally destroy cells. However, with pro-chelators, the cells are surviving.