New Compound May Have Therapeutic Benefits for FA, Other Neurodegenerative Diseases

Researchers have identified a new compound, CT51, that can potentially protect neurons from damage in severe neurodegenerative diseases, such as Friedreich’s ataxia. It can also be used to detect iron inside cells, which could be useful for monitoring these diseases.

The study, “Development of an iron-selective antioxidant probe with protective effects on neuronal function,” was published in the journal PLOS One.

Friedreich’s ataxia is known to be caused by mutations in a gene that affects iron levels in nerve cells, leading to an accumulation of iron in cells. These can become damaged, as iron leads to the formation of toxic reactive forms of oxygen.

Excess levels of iron in cells are seen in aging brains, and are also observed in Parkinson’s and Alzheimer’s diseases. It seems that neurons are particularly sensitive to high iron levels.

Experts are now studying the potentially damaging effects of high concentrations of iron in cells that can increase the vulnerability of neurons to oxidative stress and the toxicity of environmental or naturally occurring toxins.

“Given their therapeutic potential, the identification of multifunctional compounds that suppress these damaging features is highly desirable,” researchers wrote.

They synthesized and studied the effects of the new compound, called CT51, in laboratory cultures of nerve cells, or neurons. Two types of neurons were studied: the neuroblastoma cell, a neuron taken from a kind of brain cancer that grows easily in the lab and is often used to test for toxic effects on neurons; and the hippocampal neuron, a normal neuron taken from a region of the brain known as the hippocampus. The hippocampus region is often affected in Parkinson’s, Alzheimer’s, and Huntington’s disease patients.

They found that CT51 binds iron and protected neurons from damaging toxic forms of oxygen in neuroblastoma cells. In hippocampal neurons, CT51 slowed the increase in calcium levels in response to high iron levels. CT51 appears to “mop up” excess iron, preventing it from triggering cell injury.

“Probably, CT51 protects cells from oxidative damage by two independent mechanisms, namely … by sequestering redox-active iron and … by neutralization of free radicals [molecules that contribute to cell injury and aging],” the researchers wrote.

“Iron accumulation, oxidative stress and calcium signaling dysregulation are common [characteristic] signs of several neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases, Friedreich’s ataxia, and Huntington’s disease,” they added.

The scientists said the protective properties of CT51 on cellular function “highlights its possible therapeutic use in diseases with significant oxidative, iron and calcium dysregulation.”