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同步铁/铁成像显示阿尔茨海默病小鼠脑内铁的铁蓄积。

Simultaneous Fe/Fe imaging shows Fe over Fe enrichment in Alzheimer's disease mouse brain.

机构信息

Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA.

出版信息

Sci Adv. 2023 Apr 21;9(16):eade7622. doi: 10.1126/sciadv.ade7622. Epub 2023 Apr 19.

DOI:10.1126/sciadv.ade7622
PMID:37075105
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10115418/
Abstract

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

摘要

可视化氧化还原活性金属离子，如 Fe 和 Fe 离子，对于理解它们在生物过程和人类疾病中的作用至关重要。尽管已经开发出了成像探针和技术，但仍未报道能够同时以高选择性和灵敏度在活细胞中对 Fe 和 Fe 进行成像。在这里，我们选择并开发了基于 DNAzyme 的荧光开启传感器，该传感器对 Fe 或 Fe 具有选择性，在铁死亡过程中发现 Fe/Fe 比值降低，而在阿尔茨海默病小鼠大脑中发现 Fe/Fe 比值升高。升高的 Fe/Fe 比值主要观察到在淀粉样斑块区域，表明淀粉样斑块与 Fe 和/或 Fe 向 Fe 的积累之间存在相关性。我们的传感器可以深入了解不稳定铁氧化还原循环的生物学作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b3/10115418/8e028a9aa0a1/sciadv.ade7622-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b3/10115418/f781f5dad36f/sciadv.ade7622-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b3/10115418/9a80cbf291c2/sciadv.ade7622-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b3/10115418/ca9c61dc36d9/sciadv.ade7622-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b3/10115418/8e028a9aa0a1/sciadv.ade7622-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b3/10115418/f781f5dad36f/sciadv.ade7622-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b3/10115418/9a80cbf291c2/sciadv.ade7622-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b3/10115418/ca9c61dc36d9/sciadv.ade7622-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b3/10115418/8e028a9aa0a1/sciadv.ade7622-f4.jpg

相似文献

[1]
Simultaneous Fe/Fe imaging shows Fe over Fe enrichment in Alzheimer's disease mouse brain.

Sci Adv. 2023-4-21

[2]
Label-Free In Situ Chemical Characterization of Amyloid Plaques in Human Brain Tissues.

ACS Chem Neurosci. 2024-4-3

[3]
Amyloid plaques in PSAPP mice bind less metal than plaques in human Alzheimer's disease.

Neuroimage. 2009-10-1

[4]
Virtual histology of Alzheimer's disease: Biometal entrapment within amyloid-β plaques allows for detection via X-ray phase-contrast imaging.

Acta Biomater. 2023-10-15

[5]
Redox-Active Metal Ions and Amyloid-Degrading Enzymes in Alzheimer's Disease.

Int J Mol Sci. 2021-7-19

[6]
Imaging beta amyloid aggregation and iron accumulation in Alzheimer's disease using quantitative susceptibility mapping MRI.

Neuroimage. 2019-2-7

[7]
Ternary complexes of iron, amyloid-beta, and nitrilotriacetic acid: binding affinities, redox properties, and relevance to iron-induced oxidative stress in Alzheimer's disease.

Biochemistry. 2009-8-25

[8]
Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with beta-amyloid deposits in Alzheimer's disease.

J Struct Biol. 2006-7

[9]
Simultaneous quantitative susceptibility mapping and Flutemetamol-PET suggests local correlation of iron and β-amyloid as an indicator of cognitive performance at high age.

Neuroimage. 2018-3-13

[10]
Shedding Light on the Molecular Pathology of Amyloid Plaques in Transgenic Alzheimer's Disease Mice Using Multimodal MALDI Imaging Mass Spectrometry.

ACS Chem Neurosci. 2018-5-4

引用本文的文献

[1]
Signal Transduction Strategies for DNAzyme-Based Sensing and Imaging of Metal Ions in Cells and .

Chem Biomed Imaging. 2025-3-20

[2]
Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment.

Nat Aging. 2025-8-19

[3]
A general transition metal binding aptamer following the Irving-Williams series.

Chem Sci. 2025-6-24

[4]
Development of electrochemical nanoprobe for real-time intracellular measurements of Fe during ferroptosis.

Microsyst Nanoeng. 2025-7-7

[5]
Associations Between Cortical Iron Accumulation and Memory in Patients With Amnestic Mild Cognitive Impairment and in Cognitively Normal Individuals.

Brain Behav. 2025-5

[6]
Decoding Potassium Homeostasis in Cancer Metastasis and Drug Resistance: Insights from a Highly Selective DNAzyme-Based Intracellular K Sensor.

J Am Chem Soc. 2025-5-28

[7]
Effects of iron accumulation and its chelation on oxidative stress in intracortical implants.

Acta Biomater. 2025-6-15

[8]
Analysis of human brain RNA-seq data reveals combined effects of 4 types of RNA modifications and 18 types of programmed cell death on Alzheimer's disease.

J Transl Med. 2025-4-3

[9]
Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.

Signal Transduct Target Ther. 2025-2-3

[10]
Intranasal iron administration induces iron deposition, immunoactivation, and cell-specific vulnerability in the olfactory bulb of C57BL/6 mice.

Zool Res. 2025-1-18

本文引用的文献

[1]
DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons.

ACS Cent Sci. 2021-11-24

[2]
Redox-Active Metal Ions and Amyloid-Degrading Enzymes in Alzheimer's Disease.

Int J Mol Sci. 2021-7-19

[3]
Biosensing with DNAzymes.

Chem Soc Rev. 2021-8-21

[4]
Quantification of different iron forms in the aceruloplasminemia brain to explore iron-related neurodegeneration.

Neuroimage Clin. 2021

[5]
Detection and Quantification of Tightly Bound Zn in Blood Serum Using a Photocaged Chelator and a DNAzyme Fluorescent Sensor.

Anal Chem. 2021-4-13

[6]
Oxidative Damage and Antioxidant Defense in Ferroptosis.

Front Cell Dev Biol. 2020-9-17

[7]
High-Throughput Screening for the Discovery of Iron Homeostasis Modulators Using an Extremely Sensitive Fluorescent Probe.

ACS Sens. 2020-9-25

[8]
Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(1-42).

Sci Rep. 2020-6-25

[9]
Iron dyshomeostasis, lipid peroxidation and perturbed expression of cystine/glutamate antiporter in Alzheimer's disease: Evidence of ferroptosis.

Redox Biol. 2020-5

[10]
Iron Metabolism, Ferroptosis, and the Links With Alzheimer's Disease.

Front Neurosci. 2020-1-29

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