DNAzyme Sensor Used to Visualize Redox-Active Metal Ions

Researchers from The University of Texas at Austin and the University of Illinois at Urbana-Champaign  developed a new imaging technique, which has shown that in the same regions of the brain where the amyloid beta plaques associated with Alzheimer’s occur, there is also an increase in iron redox. Their imaging probe could yield even more details about the causes of Alzheimer’s and help in the search for new drugs to treat it.

“The link between iron redox and Alzheimer’s disease has been a black box,” said Yi Lu, corresponding author of the paper  published in Science Advances. “The most exciting part to me is that we now have a way to shine light into this black box so that we can begin to understand this whole process in much more detail.”

For the study, the researchers developed DNA-based fluorescent sensors that can detect two different forms of iron (Fe²⁺ and Fe³⁺) at the same time in cell cultures and in brain slices from mice genetically modified to mimic Alzheimer’s. One sensor glows green for Fe²⁺ and the other glows red for Fe³⁺. According to the team, this is the first imaging technique that can simultaneously detect both forms of iron in cells and tissue while also indicating their quantity and spatial distribution.

“The best part about our sensor is that we can now visualize the changes of Fe²⁺ and Fe³⁺ and their ratios in each location,” added first author Yuting Wu. “We can change one parameter at a time to see if it changes the plaques or the oxidative states of iron.”

That ability could help them better understand why there is an increased ratio of Fe³⁺ to Fe²⁺ in the location of amyloid beta plaques and whether increased iron redox is involved in forming the plaques.

Another key question is whether the iron redox is directly involved in cell death in Alzheimer’s, or simply a byproduct. The researchers plan to explore this question in Alzheimer’s mice. If further research determines that iron and its redox changes indeed cause cell death in Alzheimer’s patients, that information could provide a potential new strategy for drug development.