Journal ArticleDOI
Brain iron transport.
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TLDR
Key findings on brain iron transport are reviewed, highlighting the mechanisms involved in iron transport across the luminal (apical) membrane of the capillary endothelium and the membranes of different brain cell types, and iron uptake and release in neurons, oligodendrocytes, astrocyte and microglia within the brain.Abstract:
Brain iron is a crucial participant and regulator of normal physiological activity. However, excess iron is involved in the formation of free radicals, and has been associated with oxidative damage to neuronal and other brain cells. Abnormally high brain iron levels have been observed in various neurodegenerative diseases, including neurodegeneration with brain iron accumulation, Alzheimer's disease, Parkinson's disease and Huntington's disease. However, the key question of why iron levels increase in the relevant regions of the brain remains to be answered. A full understanding of the homeostatic mechanisms involved in brain iron transport and metabolism is therefore critical not only for elucidating the pathophysiological mechanisms responsible for excess iron accumulation in the brain but also for developing pharmacological interventions to disrupt the chain of pathological events occurring in these neurodegenerative diseases. Numerous studies have been conducted, but to date no effort to synthesize these studies and ideas into a systematic and coherent summary has been made, especially concerning iron transport across the luminal (apical) membrane of the capillary endothelium and the membranes of different brain cell types. Herein, we review key findings on brain iron transport, highlighting the mechanisms involved in iron transport across the luminal (apical) as well as the abluminal (basal) membrane of the blood-brain barrier, the blood-cerebrospinal fluid barrier, and iron uptake and release in neurons, oligodendrocytes, astrocytes and microglia within the brain. We offer suggestions for addressing the many important gaps in our understanding of this important topic, and provide new insights into the potential causes of abnormally increased iron levels in regions of the brain in neurodegenerative disorders.read more
Citations
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Journal ArticleDOI
Iron Metabolism, Ferroptosis, and the Links With Alzheimer's Disease.
Nao Yan,Junjian Zhang +1 more
TL;DR: The current knowledge of iron metabolism and ferroptosis is summarized, a newly defined iron-dependent form of cell death, which is distinct from apoptosis, necrosis, autophagy, and other forms ofcell death, is reviewed, and the contributions of iron and ferraptosis to AD are reviewed.
Journal ArticleDOI
Inflaming the Brain with Iron
TL;DR: Findings that connect neuroinflammation and iron accumulation are summarized, which support their causal association in the neurodegenerative processes observed in AD and PD.
Journal ArticleDOI
Hepcidin and its therapeutic potential in neurodegenerative disorders
TL;DR: This review focuses on the discussion of the therapeutic potential of hepcidin in iron‐associated neurodegenerative diseases and provides a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neuro degenerative disorders.
Journal ArticleDOI
Astrocytes in heavy metal neurotoxicity and neurodegeneration.
Baoman Li,Maosheng Xia,Robert Zorec,Vladimir Parpura,Alexei Verkhratsky,Alexei Verkhratsky,Alexei Verkhratsky +6 more
TL;DR: In this article, the authors provide a concise outlook on heavy metal-induced astrogliopathies and their association with major neurodegenerative disorders, focusing on astroglial mechanisms of iron-induced neurotoxicity.
Journal ArticleDOI
Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?
TL;DR: The review explored the deep connection between iron dysregulation and AD pathogenesis, discussed the potential of new hypothesis related to iron dyshomeostasis and ferroptosis, and summarized the therapeutics capable of targeting iron, with the expectation to draw more attention of iron Dysregulation and corresponding drug development.
References
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Structure and function of the blood–brain barrier
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TL;DR: An anatomically distinct clearing system in the brain that serves a lymphatic-like function is described and may have relevance for understanding or treating neurodegenerative diseases that involve the mis-accumulation of soluble proteins, such as amyloid β in Alzheimer's disease.
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Cloning and characterization of a mammalian proton-coupled metal-ion transporter
Hiromi Gunshin,Bryan Mackenzie,Urs V. Berger,Yoshimi Gunshin,Michael F. Romero,Walter F. Boron,Stephan Nussberger,John L. Gollan,Matthias A. Hediger +8 more
TL;DR: A new metal-ion transporter in the rat, DCT1, which has an unusually broad substrate range that includes Fe2+, Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+ and Pb2+.
Journal ArticleDOI
Structural and functional features of central nervous system lymphatic vessels
Antoine Louveau,Igor Smirnov,Timothy J. Keyes,Jacob D. Eccles,Sherin J. Rouhani,J. David Peske,Noël C. Derecki,David Castle,James Mandell,Kevin S. Lee,Tajie H. Harris,Jonathan Kipnis +11 more
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