Journal
JOURNAL OF NEUROCHEMISTRY
Volume 165, Issue 5, Pages 625-642Publisher
WILEY
DOI: 10.1111/jnc.15819
Keywords
blood-brain barrier; brain iron; h-ferritin; neurodegeneration; regulation; transferrin
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Brain iron homeostasis is crucial for neurological health, and its imbalance is associated with various neurological disorders. Proper regulation of iron entry into the brain via transferrin and H-ferritin is important due to the detrimental effects of unrestricted iron. This review discusses the mechanisms of iron transport regulation at the blood-brain barrier and explores the dysregulation of brain iron in Alzheimer's disease, Parkinson's disease, and restless legs syndrome.
Brain iron homeostasis is crucial for neurological health, with pathological fluctuations in brain iron levels associated with a variety of neurological disorders. Low levels are connected to cognitive impairment and restless legs syndrome, while high levels are connected to Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Given the detrimental effects unrestricted iron can have, regulated entry into the brain via transferrin and H-ferritin is critical. Endothelial cells of the blood-brain barrier are the site of iron transport regulation. The movement of iron through endothelial cells into the brain can be divided into three distinct processes: uptake, transcytosis, and release. Each process possesses external and internal influences on the regulation at each stage. This review discusses the mechanisms of iron uptake, transcytosis, and release at the blood-brain barrier, as well as the elements that contribute to regulation. Additionally, we explore the dysregulation of brain iron in Alzheimer's disease, Parkinson's disease, and restless legs syndrome.
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