Related Experiment Video
Updated: May 29, 2025
Setup of Capillary Electrophoresis-Inductively Coupled Plasma Mass Spectrometry CE-ICP-MS for Quantification of Iron Redox Species FeII, FeIII
Published on: May 4, 2020
Iron chelation by oral deferoxamine treatment decreased brain iron and iron signaling proteins
Max A Thorwald1, Naomi S Sta Maria2,3, Ararat Chakhoyan2,3
1Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Background:
Deferoxamine (DFO) and other iron chelators are clinically used for cancer and stroke. They may also be useful for Alzheimer's disease (AD) to diminish iron from microbleeds. DFO may also stimulate antioxidant membrane repair which is impaired during AD. DFO and other chelators do enter the brain despite some contrary reports.
Objective:
Low dose, oral DFO was given in lab chow to wildtype (WT) C57BL/6 mice to evaluate potential impact on iron levels, iron-signaling and storage proteins, and amyloid-β protein precursor (AβPP) and processing enzymes. Young WT mice do not have microbleeds or disrupted blood-brain barrier of AD mice.
Methods:
Iron was measured by MRI and chemically after two weeks of dietary DFO. Cerebral cortex was examined for changes in iron metabolism, antioxidant signaling, and AβPP processing by western blot.
Results:
DFO decreased brain iron 18% (p < 0.01) estimated by R2 MRI and decreased seven major proteins that mediate iron metabolism by at least 25%. The iron storage proteins ferritin light and heavy chain decreased by at least 30%. AβPP and secretase enzymes also decreased by 30%.
Conclusions:
WT mice respond to DFO with decreased AβPP, amyloid processing enzymes, and antioxidant repair. Potential DFO treatment for early-stage AD by DFO should consider the benefits of lowered AβPP and secretase enzymes.
