scholarly journals Alteration of Iron Concentration in Alzheimer’s Disease as a Possible Diagnostic Biomarker Unveiling Ferroptosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4479
Author(s):  
Eleonora Ficiarà ◽  
Zunaira Munir ◽  
Silvia Boschi ◽  
Maria Eugenia Caligiuri ◽  
Caterina Guiot
Keyword(s):  
Iron Transport ◽  
Biological Fluids ◽  
Iron Status ◽  
Iron Concentration ◽  
Diagnostic Biomarker ◽  
Resonance Imaging ◽  
Brain Iron ◽  
Indirect Measurements ◽  
Brain Iron Metabolism ◽  
The Brain

Proper functioning of all organs, including the brain, requires iron. It is present in different forms in biological fluids, and alterations in its distribution can induce oxidative stress and neurodegeneration. However, the clinical parameters normally used for monitoring iron concentration in biological fluids (i.e., serum and cerebrospinal fluid) can hardly detect the quantity of circulating iron, while indirect measurements, e.g., magnetic resonance imaging, require further validation. This review summarizes the mechanisms involved in brain iron metabolism, homeostasis, and iron imbalance caused by alterations detectable by standard and non-standard indicators of iron status. These indicators for iron transport, storage, and metabolism can help to understand which biomarkers can better detect iron imbalances responsible for neurodegenerative diseases.

scholarly journals A role for sex and a common HFE gene variant in brain iron uptake

2017 ◽  
Vol 38 (3) ◽  
pp. 540-548 ◽  
Author(s):  
Kari A Duck ◽  
Elizabeth B Neely ◽  
Ian A Simpson ◽  
James R Connor
Keyword(s):  
Blood Brain Barrier ◽  
Iron Uptake ◽  
Iron Transport ◽  
Iron Status ◽  
Brain Barrier ◽  
Hfe Gene ◽  
Brain Iron ◽  
Cellular Iron ◽  
Blood Brain ◽  
The Brain

HFE (high iron) is an essential protein for regulating iron transport into cells. Mutations of the HFE gene result in loss of this regulation causing accumulation of iron within the cell. The mutated protein has been found increasingly in numerous neurodegenerative disorders in which increased levels of iron in the brain are reported. Additionally, evidence that these mutations are associated with elevated brain iron challenges the paradigm that the brain is protected by the blood–brain barrier. While much has been studied regarding the role of HFE in cellular iron uptake, it has remained unclear what role the protein plays in the transport of iron into the brain. We investigated regulation of iron transport into the brain using a mouse model with a mutation in the HFE gene. We demonstrated that the rate of radiolabeled iron (59Fe) uptake was similar between the two genotypes despite higher brain iron concentrations in the mutant. However, there were significant differences in iron uptake between males and females regardless of genotype. These data indicate that brain iron status is consistently maintained and tightly regulated at the level of the blood–brain barrier.

scholarly journals Regulation of the Profile of Iron-Management Proteins in Brain Microvasculature

2004 ◽  
Vol 24 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Joseph R. Burdo ◽  
Ian A. Simpson ◽  
Sharon Menzies ◽  
John Beard ◽  
James R. Connor
Keyword(s):  
Iron Transport ◽  
Iron Status ◽  
Protein Profile ◽  
Brain Iron ◽  
Divalent Metal Transporter 1 ◽  
Iron Storage ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Brain Microvasculature ◽  
The Brain

The distribution of brain iron is heterogeneous, but the mechanism by which these regional differences are achieved and maintained is unknown. In this study, the authors test two hypotheses related to brain iron transport. The first is that there is regional variability in the profile of proteins associated with iron transport and storage in the brain microvasculature. The second hypothesis is that the iron status of the brain will dictate the response of the protein profile in the microvasculature to changes in systemic iron status. The profile analysis consists of transferrin (iron transport), ferritin (iron storage), transferrin receptor (iron uptake), and divalent metal transporter 1 (release of iron from endosomes). An additional protein involved in cellular iron efflux, ferroportin, was not detected in brain microvasculature. The results show that there are significantly higher levels of these proteins in the microvasculature from each area of the brain compared to a whole brain homogenate, but no regional differences within the microvasculature. The levels of ferritin observed in the microvasculature indicate that the microvascular endothelial cells have significant iron storage capacity. There are no significant changes in the regional protein profiles in response to systemic iron manipulation when brain iron status was normal. In contrast, in Belgrade rats, whose brain is iron deficient, the expression of both divalent metal transporter 1 and transferrin receptor was increased compared with control in almost all brain regions examined, but not transferrin or ferritin. These findings indicate that regional brain iron heterogeneity is not maintained by differences in microvascular iron-management protein levels. The results also indicate that brain iron status dictates the response of the microvascular protein profile to systemic iron manipulation.

scholarly journals Hepcidin overexpression in astrocytes alters brain iron metabolism and protects against amyloid-β induced brain damage in mice

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Xinwei Zhang ◽  
Yu-Jing Gou ◽  
Yating Zhang ◽  
Jie Li ◽  
Kang Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Metabolism ◽  
Cell Damage ◽  
Amyloid Β ◽  
Protective Role ◽  
Iron Level ◽  
Brain Iron ◽  
Brain Iron Metabolism ◽  
The Brain

Abstract Progressive iron accumulation in the brain and iron-induced oxidative stress are considered to be one of the initial causes of Alzheimer’s disease (AD), and modulation of brain iron level shows promise for its treatment. Hepcidin expressed by astrocytes has been speculated to regulate iron transport across the blood–brain barrier (BBB) and control the whole brain iron load. Whether increasing the expression of astrocyte hepcidin can reduce brain iron level and relieve AD symptoms has yet to be studied. Here, we overexpressed hepcidin in astrocytes of the mouse brain and challenged the mice with amyloid-β25–35 (Aβ25–35) by intracerebroventricular injection. Our results revealed that hepcidin overexpression in astrocytes significantly ameliorated Aβ25–35-induced cell damage in both the cerebral cortex and hippocampus. This protective role was also attested by behavioral tests of the mice. Our data further demonstrated that astrocyte-overexpressed hepcidin could decrease brain iron level, possibly by acting on ferroportin 1 (FPN1) on the brain microvascular endothelial cells (BMVECs), which in turn reduced Aβ25–35-induced oxidative stress and apoptosis, and ultimately protected cells from damage. This study provided in vivo evidences of the important role of astrocyte hepcidin in the regulation of brain iron metabolism and protection against Aβ-induced cortical and hippocampal damages and implied its potential in the treatment of oxidative stress-related brain disorders.

scholarly journals Endothelial cells are critical regulators of iron transport in a model of the human blood–brain barrier

2018 ◽  
Vol 39 (11) ◽  
pp. 2117-2131 ◽  
Author(s):  
Brian Chiou ◽  
Emma H Neal ◽  
Aaron B Bowman ◽  
Ethan S Lippmann ◽  
Ian A Simpson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Iron Deficiency ◽  
Blood Brain Barrier ◽  
Iron Transport ◽  
Brain Barrier ◽  
Brain Iron ◽  
Blood Brain ◽  
Iron Delivery ◽  
The Impact ◽  
The Brain

Iron delivery to the brain is essential for multiple neurological processes such as myelination, neurotransmitter synthesis, and energy production. Loss of brain iron homeostasis is a significant factor in multiple neurological disorders. Understanding the mechanism by which the transport of iron across the blood–brain barrier (BBB) is regulated is crucial to address the impact of iron deficiency on brain development and excessive accumulation of iron in neurodegenerative diseases. Using induced pluripotent stem cell (iPSC)-derived brain endothelial cells (huECs) as a human BBB model, we demonstrate the ability of transferrin, hepcidin, and DMT1 to impact iron transport and release. Our model reveals a new function for H-ferritin to transport iron across the BBB by binding to the T-cell immunoglobulin and mucin receptor 1. We show that huECs secrete both transferrin and H-ferritin, which can serve as iron sources for the brain. Based on our data, brain iron status can exert control of iron transport across the endothelial cells that constitute the BBB. These data address a number of pertinent questions such as how brain iron uptake is regulated at the regional level, the source of iron delivery to the brain, and the clinical strategies for attempting to treat brain iron deficiency.

Сauses of Dizziness in Patients with Suspected Stroke

2018 ◽  
Vol 7 (3) ◽  
pp. 217-221
Author(s):  
E. V. Shevchenko ◽  
G. R. Ramazanov ◽  
S. S. Petrikov
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Demyelinating Disease ◽  
Heart Rhythm ◽  
Diagnostic Methods ◽  
Deficiency Anemia ◽  
Resonance Imaging ◽  
Peripheral Vestibulopathy ◽  
Suspected Stroke ◽  
The Brain

Background Acute dizziness may be the only symptom of stroke. Prevalence of this disease among patients with isolated dizziness differs significantly and depends on study design, inclusion criteria and diagnostic methods. In available investigations, we did not find any prospective studies where magnetic resonance imaging, positional maneuvers, and Halmagyi-Curthoys test had been used to clarify a pattern of diseases with isolated acute dizziness and suspected stroke.Aim of study To clarify the pattern of the causes of dizziness in patients with suspected acute stroke.Material and methods We examined 160 patients admitted to N.V. Sklifosovsky Research Institute for Emergency Medicine with suspected stroke and single or underlying complaint of dizziness. All patients were examined with assessment of neurological status, Dix-Hollpike and Pagnini-McClure maneuvers, HalmagyiCurthoys test, triplex scans of brachiocephalic arteries, transthoracic echocardiography, computed tomography (CT) and magnetic resonance imaging (MRI) of the brain with magnetic field strength 1.5 T. MRI of the brain was performed in patients without evidence of stroke by CT and in patients with stroke of undetermined etiology according to the TOAST classification.Results In 16 patients (10%), the cause of dizziness was a disease of the brain: ischemic stroke (n=14 (88%)), hemorrhage (n=1 (6%)), transient ischemic attack (TIA) of posterior circulation (n=1 (6%)). In 70.6% patients (n=113), the dizziness was associated with peripheral vestibulopathy: benign paroxysmal positional vertigo (n=85 (75%)), vestibular neuritis (n=19 (17%)), Meniere’s disease (n=7 (6%)), labyrinthitis (n=2 (1,3%)). In 6.9% patients (n=11), the cause of dizziness was hypertensive encephalopathy, 1.9% of patients (n=3) had heart rhythm disturbance, 9.4% of patients (n=15) had psychogenic dizziness, 0.6% of patients (n=1) had demyelinating disease, and 0.6% of patients (n=1) had hemic hypoxia associated with iron deficiency anemia.Conclusion In 70.6% patients with acute dizziness, admitted to hospital with a suspected stroke, peripheral vestibulopathy was revealed. Only 10% of patients had a stroke as a cause of dizziness.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

Neurometabolic Diseases in Children: Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy Features

2019 ◽  
Vol 15 (3) ◽  
pp. 255-268
Author(s):  
Direnç Özlem Aksoy ◽  
Alpay Alkan
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Metabolic Pathways ◽  
Wide Spectrum ◽  
Demyelinating Diseases ◽  
Resonance Spectroscopy ◽  
Resonance Imaging ◽  
Neurometabolic Disorders ◽  
Brain Involvement ◽  
The Brain

Background: Neurometabolic diseases are a group of diseases secondary to disorders in different metabolic pathways, which lead to white and/or gray matter of the brain involvement. </P><P> Discussion: Neurometabolic disorders are divided in two groups as dysmyelinating and demyelinating diseases. Because of wide spectrum of these disorders, there are many different classifications of neurometabolic diseases. We used the classification according to brain involvement areas. In radiological evaluation, MRI provides useful information for these disseases. Conclusion: Magnetic Resonance Spectroscopy (MRS) provides additional metabolic information for diagnosis and follow ups in childhood with neurometabolic diseases.

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