{"id":333,"date":"2023-05-01T15:01:44","date_gmt":"2023-05-01T15:01:44","guid":{"rendered":"http:\/\/thisbiginfluence.com\/?p=333"},"modified":"2023-05-01T15:01:44","modified_gmt":"2023-05-01T15:01:44","slug":"irons-surprising-role-in-alzheimers-uncovered","status":"publish","type":"post","link":"https:\/\/thisbiginfluence.com\/?p=333","title":{"rendered":"Iron\u2019s Surprising Role in Alzheimer\u2019s Uncovered"},"content":{"rendered":"


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Researchers have found a doable hyperlink between iron within the mind and Alzheimer\u2019s illness utilizing a brand new imaging probe. This breakthrough might present new insights into the function of iron in Alzheimer\u2019s and information the event of latest remedies focusing on iron redox adjustments.<\/p>\n

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What if amyloid beta plaques aren\u2019t the principle reason for Alzheimer\u2019s<\/span> disease?<\/strong><\/p>\n

There is a growing body of evidence that iron in the brain may play a role in Alzheimer\u2019s disease. Lending weight to that idea, a new imaging probe has for the first time shown that in the same regions of the brain where the amyloid beta plaques associated with Alzheimer\u2019s occur, there is also an increase in iron redox, meaning the iron in these regions is more reactive in the presence of oxygen. Their imaging probe could yield even more details about the causes of Alzheimer\u2019s and help in the search for new drugs to treat it.<\/p>\n

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A team from The University of Texas at Austin<\/a> and the University of Illinois at Urbana-Champaign<\/a> published a study on the new imaging technique and findings in Science Advances<\/span><\/em>.<\/p>\n

\u201cThe link between iron redox and Alzheimer\u2019s disease has been a black box,\u201d said Yi Lu, corresponding author and professor of chemistry at UT Austin. \u201cThe 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.\u201d<\/p>\n

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Schematic of a novel iron sensor. When a short strand of DNA called a DNAzyme (green) binds to a specific form of iron (e.g., Fe3+ or Fe2+), the DNAzyme cuts a second strand of DNA (red) and releases a fluorescent signal (yellow) that indicates visually the presence of the specific form of iron. Credit: David Steadman\/University of Texas at Austin<\/p>\n

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About a decade ago, scientists discovered ferroptosis, a process in the body that is dependent on elevated iron levels, leads to cell death and plays a key role in neurodegenerative diseases, such as Alzheimer\u2019s. Using magnetic resonance imaging on living Alzheimer\u2019s patients, scientists have observed that these patients tend to have elevated iron levels in the brain, although that method doesn\u2019t differentiate between different forms of iron. Together, these findings suggested that iron might play a role in destroying brain cells in Alzheimer\u2019s patients.<\/p>\n

For the new study, the researchers developed DNA<\/span>-based fluorescent sensors that can detect two different forms of iron (Fe2+<\/sup> and Fe3+<\/sup>) at the same time in cell cultures and in brain slices from mice genetically modified to mimic Alzheimer\u2019s. One sensor glows green for Fe2+<\/sup> and the other glows red for Fe3+<\/sup>. 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.<\/p>\n

\u201cThe best part about our sensor is that we can now visualize the changes of Fe2+<\/sup> and Fe3+<\/sup> and their ratios in each location,\u201d said Yuting Wu, a co-first author of the study and a postdoctoral researcher in Lu\u2019s lab at UT Austin. \u201cWe can change one parameter at a time to see if it changes the plaques or the oxidative states of iron.\u201d<\/p>\n

\"Increases<\/p>\n

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\u2019s (green image at right). One sensor glows green for Fe2+ and the other glows red for Fe3+. This method has for the first time shown that in the same regions of the brain where the amyloid beta plaques associated with Alzheimer\u2019s occur (blue), there is also an increase in the ratio of Fe2+ and Fe3+. Credit: University of Texas at Austin<\/p>\n

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That ability could help them better understand why there is an increased ratio of Fe3+<\/sup>\u00a0to Fe2+<\/sup> in the location of amyloid beta plaques and whether increased iron redox is involved in forming the plaques.<\/p>\n

Another key question is whether the iron redox is directly involved in cell death in Alzheimer\u2019s, or simply a byproduct. The researchers plan to explore this question in Alzheimer\u2019s mice. If further research determines that iron and its redox changes indeed cause cell death in Alzheimer\u2019s patients, that information could provide a potential new strategy for drug development. In other words, perhaps a drug that change the ratio Fe3+<\/sup> to Fe2+ <\/sup>could help protect brain cells. The new imaging probe could be used to test how well drug candidates work at changing the ratio.<\/p>\n

To develop the sensors, the scientists first hired a commercial lab to produce a library of 100 trillion short DNA strands, through a chemical process called oligonucleotide synthesis. They then conducted a screening process to find those strands that recognize \u2014 or in chemistry parlance \u201cbind tightly to and conduct a catalytic reaction with\u201d \u2014 a specific form of iron and not any other forms. To complete the sensors, other components were added including molecules called fluorophores that glow in a specific color when the probe recognizes the specific form of iron.<\/p>\n

Reference: \u201cSimultaneous Fe2+<\/sup>\/Fe3+<\/sup> imaging shows Fe3+<\/sup> over Fe2+<\/sup> enrichment in Alzheimer\u2019s disease mouse brain\u201d by uting Wu, Seyed-Fakhreddin Torabi, Ryan J. Lake, Shanni Hong, Zhengxin Yu, Peiwen Wu, Zhenglin Yang, Kevin Nelson, Weijie Guo, Gregory T. Pawel, Jacqueline Van Stappen, Xiangli Shao, Liviu M. Mirica and Yi Lu, 19 April 2023, Science Advances<\/em>.
DOI: 10.1126\/sciadv.ade7622<\/a><\/p>\n

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Lu, who moved his lab to UT Austin from the University of Illinois at Urbana-Champaign in the summer of 2021, collaborated with researchers there including professor of chemistry Liviu Mirica.<\/p>\n

This work was supported by the National Institutes of Health, the Alzheimer\u2019s Association and the Robert A. Welch Foundation. Lu holds the Richard J.V. Johnson \u2013 Welch Regents Chair in Chemistry.<\/p>\n

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