Thorwald Max A, Sta Maria Naomi S, Chakhoyan Ararat, O'Day Peggy A, Jacobs Russell E, Zlokovic Berislav, Finch Caleb E
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
J Alzheimers Dis. 2025 Feb;103(4):1180-1190. doi: 10.1177/13872877241313031. Epub 2025 Feb 2.
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.
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.
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.
DFO decreased brain iron 18% ( < 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%.
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.
去铁胺（DFO）和其他铁螯合剂在临床上用于治疗癌症和中风。它们可能对阿尔茨海默病（AD）也有用，可减少微出血中的铁。DFO还可能刺激抗氧化膜修复，而这在AD期间受损。尽管有一些相反的报道，但DFO和其他螯合剂确实会进入大脑。
给野生型（WT）C57BL/6小鼠喂食含低剂量口服DFO的实验室饲料，以评估其对铁水平、铁信号和储存蛋白以及淀粉样β蛋白前体（AβPP）和加工酶的潜在影响。年轻的WT小鼠没有AD小鼠的微出血或血脑屏障破坏。
在饮食中添加DFO两周后，通过MRI和化学方法测量铁含量。通过蛋白质印迹法检查大脑皮层中铁代谢、抗氧化信号和AβPP加工的变化。
通过R2 MRI估计，DFO使脑铁含量降低了18%（<0.01），并使七种介导铁代谢的主要蛋白质减少了至少25%。铁储存蛋白轻链和重链铁蛋白至少降低了30%。AβPP和分泌酶也降低了30%。
WT小鼠对DFO的反应是AβPP、淀粉样蛋白加工酶和抗氧化修复减少。DFO对早期AD的潜在治疗应考虑降低AβPP和分泌酶的益处。
