TY - JOUR
T1 - Brain Iron Dysregulation in Iron Deficiency Anemia-Related Restless Leg Syndrome Revealed by Neuron-Derived Extracellular Vesicles
T2 - A Case–Control Study
AU - Manolopoulos, Apostolos
AU - York, William
AU - Pucha, Krishna Ananthu
AU - Earley, Christopher J.
AU - Kapogiannis, Dimitrios
N1 - Publisher Copyright:
© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
PY - 2024/9
Y1 - 2024/9
N2 - 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.
AB - 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.
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U2 - 10.1002/ana.26941
DO - 10.1002/ana.26941
M3 - Article
C2 - 38646966
AN - SCOPUS:85191201545
SN - 0364-5134
VL - 96
SP - 560
EP - 564
JO - Annals of neurology
JF - Annals of neurology
IS - 3
ER -