Brain Iron Dysregulation in Iron Deficiency Anemia-Related Restless Leg Syndrome Revealed by Neuron-Derived Extracellular Vesicles: A Case-Control Study.
Brain Iron Dysregulation in Iron Deficiency Anemia-Related Restless Leg Syndrome Revealed by Neuron-Derived Extracellular Vesicles: A Case-Control Study.
复制标题
神经元衍生的细胞外囊泡揭示了缺铁性贫血相关的不宁腿综合征中的脑铁失调：病例对照研究。
DOI：
10.1002/ana.26941
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发表时间：
2024
影响因子：
11.2
通讯作者：
Kapogiannis,Dimitrios
中科院分区：
文献类型：
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作者：
Manolopoulos,Apostolos;York,William;Pucha,KrishnaAnanthu;Earley,ChristopherJ;Kapogiannis,Dimitrios
脑铁缺乏（ID），并在一定程度上，全身ID已牵连在不宁腿综合征（RLS）的发病机制。以前，我们发现RLS中神经元源性细胞外囊泡（NDEV）中的铁蛋白增加，这表明通过分泌负载铁蛋白的NDEV消耗细胞内铁的机制。在这项研究中，我们假设，增加NDEV铁蛋白发生，甚至在RLS伴随全身性ID和神经元细胞内铁耗竭在RLS也表现为NDEV异常的其他铁调节蛋白，特别是，减少转铁蛋白受体（TfR）和增加ferroportin。为了解决这些假设，我们研究了71例ID贫血，36例RLS和35例无RLS的女性。RLS受试者再次显示出较高的NDEV铁蛋白，也降低了TfR，这表明减少了神经元的铁摄取能力。研究结果为更全面地了解神经元铁稳态的致病作用提供了信息，并将其与外周ID分离。ANN NEUROL 2024;96：560-564
Brain iron deficiency (ID) and, to a degree, systemic ID have been implicated in restless leg syndrome (RLS) pathogenesis. Previously, we found increased ferritin in neuron‐derived extracellular vesicles (NDEVs) in RLS, suggesting a mechanism for depleting intracellular iron by secreting ferritin‐loaded NDEVs. In this study, we hypothesized that increased NDEV ferritin occurs even in RLS accompanied by systemic ID and that neuronal intracellular iron depletion in RLS also manifests as NDEV abnormalities in other iron regulatory proteins, specifically, decreased transferrin receptor (TfR) and increased ferroportin. To address these hypotheses, we studied 71 women with ID anemia, 36 with RLS, and 35 without RLS. Subjects with RLS again showed higher NDEV ferritin and also decreased TfR, suggesting diminished neuronal capacity for iron uptake. Findings inform a more complete understanding of the pathogenic role of neuronal iron homeostasis and dissociate it from peripheral ID. ANN NEUROL 2024;96:560–564