Simultaneous Fe ²⁺ /Fe ³⁺ imaging shows Fe ³⁺ over Fe ²⁺ enrichment in Alzheimer’s disease mouse brain

Abstract

Visualizing redox-active metal ions, such as Fe 2+ and Fe 3+ ions, are essential for understanding their roles in biological processes and human diseases. Despite the development of imaging probes and techniques, imaging both Fe 2+ and Fe 3+ 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 Fe 2+ or Fe 3+ , revealing a decreased Fe 3+ /Fe 2+ ratio during ferroptosis and an increased Fe 3+ /Fe 2+ ratio in Alzheimer’s disease mouse brain. The elevated Fe 3+ /Fe 2+ ratio was mainly observed in amyloid plaque regions, suggesting a correlation between amyloid plaques and the accumulation of Fe 3+ and/or conversion of Fe 2+ to Fe 3+ . Our sensors can provide deep insights into the biological roles of labile iron redox cycling.

Iron scavenging and suppression of collagen cross-linking underlie antifibrotic effects of carnosine in the heart with obesity

“…Given the known link between lipid peroxidation and ferroptosis, it is notable that a higher Fe 3+ /Fe 2+ ratio was found to be associated with ferroptosis in serum of Eales disease patients and in the amyloid plaque regains of mouse brains in an Alzheimers' model. Both conditions are associated with lipid peroxidation and advanced glycation end product (AGE) accumulation (Swamy-Mruthinti et al, 2002;Selvi et al, 2007;Wu et al, 2023). However, the prooxidant effect of iron in these studies is typically examined in the context of total iron levels rather than reporting the Fe 3+ /Fe 2+ ratio, which makes the in vivo and translational significance of this observation somewhat limited.…”