Here is an experimental AD paper telling what happens with Fe2+/Fe3+.

Sci Adv

. 2023 Apr 21;9(16):eade7622.

doi: 10.1126/sciadv.ade7622. Epub 2023 Apr 19.

Simultaneous Fe²⁺/Fe³⁺ imaging shows Fe³⁺ over Fe²⁺ enrichment in Alzheimer's disease mouse brain

Yuting Wu ^{1 2}, Seyed-Fakhreddin Torabi ³, Ryan J Lake ¹, Shanni Hong ¹, Zhengxin Yu ¹, Peiwen Wu ³, Zhenglin Yang ^{2 3}, Kevin Nelson ³, Weijie Guo ^{3 4}, Gregory T Pawel ¹, Jacqueline Van Stappen ², Xiangli Shao ^{1 2}, Liviu M Mirica ¹, Yi Lu ^{1 2 3 4}

Affiliations Expand

• PMID: 37075105

PMCID: PMC10115418 DOI: 10.1126/sciadv.ade7622

Abstract

Visualizing redox-active metal ions, such as Fe²⁺ and Fe³⁺ ions, are essential for understanding their roles in biological processes and human diseases. Despite the development of imaging probes and techniques, imaging both Fe²⁺ and Fe³⁺ simultaneously in living cells with high selectivity and sensitivity has not been reported. Here, we selected and developed DNAzyme-based fluorescent turn-on sensors that are selective for either Fe²⁺ or Fe³⁺, revealing a decreased Fe³⁺/Fe²⁺ ratio during ferroptosis and an increased Fe³⁺/Fe²⁺ ratio in Alzheimer's disease mouse brain. The elevated Fe³⁺/Fe²⁺ ratio was mainly observed in amyloid plaque regions, suggesting a correlation between amyloid plaques and the accumulation of Fe³⁺ and/or conversion of Fe²⁺ to Fe³⁺. Our sensors can provide deep insights into the biological roles of labile iron redox cycling.



Now let us look at the abstract of the Pall et al paper once again, the end of it:

"ATH434 significantly stabilized bound Fe2+ from ligand-induced autooxidation, reducing reactive oxygen species (ROS) production, whereas DFP and DFX promoted production. The comparable affinity of ATH434 for Fe2+ and Fe3+ position it to sequester excess Fe2+ and facilitate drug-to-protein iron metal exchange, at a reduced risk of autooxidation-induced ROS generation or perturbation of cellular iron stores".

Here is the Pall et al paper if you want to go back to it: https://pubmed.ncbi.nlm.nih.gov/39317669/