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iron in the brain

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https://www.readbyqxmd.com/read/28821470/design-of-the-drepagreffe-trial-a-prospective-controlled-multicenter-study-evaluating-the-benefit-of-genoidentical-hematopoietic-stem-cell-transplantation-over-chronic-transfusion-in-sickle-cell-anemia-children-detected-to-be-at-risk-of-stroke-by-transcranial
#1
Sylvie Chevret, Suzanne Verlhac, Elisabeth Ducros-Miralles, Jean-Hugues Dalle, Regis Peffault de Latour, Mariane de Montalembert, Malika Benkerrou, Corinne Pondarré, Isabelle Thuret, Corinne Guitton, Emmanuelle Lesprit, Maryse Etienne-Julan, Gisèle Elana, Jean-Pierre Vannier, Patrick Lutz, Bénédicte Neven, Claire Galambrun, Catherine Paillard, Camille Runel, Charlotte Jubert, Cécile Arnaud, Annie Kamdem, Valentine Brousse, Florence Missud, Marie Petras, Lydia Doumdo-Divialle, Claire Berger, Françoise Fréard, Olivier Taieb, Elise Drain, Monique Elmaleh, Manuela Vasile, Yacine Khelif, Myriam Bernaudin, Philippe Chadebech, France Pirenne, Gérard Socié, Françoise Bernaudin
BACKGROUND: Children with sickle cell anemia (SCA) have an 11% risk of stroke by the age of 18. Chronic transfusion applied in patients detected to be at risk by transcranial Doppler allows a significant reduction of stroke risk. However, chronic transfusion exposes to several adverse events, including alloimmunization and iron overload, and is not curative. Hematopoietic stem cell transplantation allows termination of the transfusion program, but its benefit has not been demonstrated...
August 15, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28821231/novel-mutations-in-pank2-and-pla2g6-genes-in-patients-with-neurodegenerative-disorders-two-case-reports
#2
Hassan Dastsooz, Hamid Nemati, Mohammad Ali Farazi Fard, Majid Fardaei, Mohammad Ali Faghihi
BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous group of disorders associated with progressive impairment of movement, vision, and cognition. The disease is initially diagnosed on the basis of changes in brain magnetic resonance imaging which indicate an abnormal brain iron accumulation in the basal ganglia. However, the diagnosis of specific types should be based on both clinical findings and molecular genetic testing for genes associated with different types of NBIA, including PANK2, PLA2G6, C19orf12, FA2H, ATP13A2, WDR45, COASY, FTL, CP, and DCAF17...
August 18, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28818478/mutations-in-ddhd1-encoding-a-phospholipase-a1-is-a-novel-cause-of-retinopathy-and-neurodegeneration-with-brain-iron-accumulation
#3
Rodolphe Dard, Claire Meyniel, Valérie Touitou, Giovanni Stevanin, Foudil Lamari, Alexandra Durr, Claire Ewenczyk, Fanny Mochel
Defects of phospholipids remodelling and synthesis are inborn errors of metabolism responsible for various clinical presentations including spastic paraplegia, retinopathy, optic atrophy, myo- and cardiomyopathies, and osteo-cutaneous manifestations. DDHD1 encodes a phospholipase A1, which is involved in the remodelling of phospholipids. We previously described a relatively pure hereditary spastic paraplegia (HSP) phenotype associated with mutations in DDHD1. Here we report a complex form of HSP associated with retinal dystrophy and a pattern of neurodegeneration with brain iron accumulation (NBIA) on brain MRI, due to a novel homozygous mutation in DDHD1...
August 14, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28815906/deep-gray-matter-iron-measurement-in-patients-with-liver-cirrhosis-using-quantitative-susceptibility-mapping-relationship-with-pallidal-t1-hyperintensity
#4
Song Lee, Yoonho Nam, Jinhee Jang, Gun Hyung Na, Dong Goo Kim, Na-Young Shin, Hyun Seok Choi, So-Lyung Jung, Kook-Jin Ahn, Bum-Soo Kim
BACKGROUND: The liver is a central organ for the metabolism of iron and manganese and the places where those metals are commonly deposited overlap in the brain. PURPOSE/HYPOTHESIS: To elucidate the relationship between pallidal T1 hyperintensity and iron deposition in the deep gray matter of liver cirrhosis patients using quantitative susceptibility mapping (QSM). STUDY TYPE: Retrospective case-control study SUBJECTS: In all, 38 consecutive liver cirrhosis patients who received brain magnetic resonance imaging (MRI) as pretransplant evaluation...
August 17, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28814227/mitochondrial-aconitase-in-neurodegenerative-disorders-role-of-a-metabolism-related-molecule-in-neurodegeneration
#5
Fariba Khodagholi, Fatemeh Shaerzadeh, Fateme Montazeri
Mitochondrial aconitase (Aco2), a member of the family of iron-sulfur [4Fe-4S]-containing dehydratases, is involved in cellular metabolism through the tricarboxylic acid cycle. Aco2 is highly susceptible to oxidative damage in a way that exposure to the reactive species and free radicals lead to release of iron from the central [4Fe-4S] cluster resulting in the production of the inactive form of Aco2. There is increasing evidence supporting a direct association between impaired energy metabolism and the incidence and progression of neurodegenerative disorders in neuronal cells...
August 16, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28811866/preliminary-data-on-the-interaction-between-some-biometals-and-oxidative-stress-status-in-mild-cognitive-impairment-and-alzheimer-s-disease-patients
#6
Ioana-Miruna Balmuș, Stefan-Adrian Strungaru, Alin Ciobica, Mircea-Nicusor Nicoara, Romeo Dobrin, Gabriel Plavan, Cristinel Ștefănescu
Increased interest regarding the biometal mechanisms of action and the pathways in which they have regulatory roles was lately observed. Particularly, it was shown that biometal homeostasis dysregulation may lead to neurodegeneration including Alzheimer's disease, Parkinson disease, or prion protein disease, since important molecular signaling mechanisms in brain functions implicate both oxidative stress and redox active biometals. Oxidative stress could be a result of a breakdown in metal-ion homeostasis which leads to abnormal metal protein chelation...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28811697/role-of-iron-and-copper-in-the-pathogenesis-of-parkinson-s-disease
#7
Mohit Kumar Gangania, Jyoti Batra, Suman Kushwaha, Rachna Agarwal
Parkinson's disease (PD) is an old age disorder of basal ganglia which involves oligomerization of α-synuclein protein and formation of intercellular inclusions known as "Lewy bodies" in substantia nigra and caudate nuclei in brain which is progressive in nature. It is second most prevalent neurodegenerative disorder characterized by tremor at rest, muscle rigidity, slowness of movement (bradykinesia, akinesia), and changes in posture (instability). Both excess and deficiency in levels of transition metals (especially iron, copper) can be detrimental to the central nervous system...
July 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28811225/alpha-synuclein-ferrireductase-activity-is-detectible-in-vivo-is-altered-in-parkinson-s-disease-and-increases-the-neurotoxicity-of-dopal
#8
Jennifer S McDowall, Ioanna Ntai, Kevin C Honeychurch, John P Hart, Philippe Colin, Bernard L Schneider, David R Brown
The normal cellular role of α-synuclein is of potential importance in understanding diseases in which an aggregated form of the protein has been implicated. A potential loss or change in the normal function of α-synuclein could play a role in the aetiology of diseases such as Parkinson's disease. Recently, it has been suggested that α-synuclein could cause the enzymatic reduction of iron and a cellular increase in Fe(II) levels. Experiments were carried out to determine if such activity could be measured in vivo...
August 12, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28808954/heavy-metal-pollutants-in-selected-organs-of-african-giant-rats-from-three-agro-ecological-zones-of-nigeria-evidence-for-their-role-as-an-environmental-specimen-bank
#9
Ifukibot Levi Usende, Benjamin O Emikpe, James Olukayode Olopade
An assessment of the concentration of heavy metals in the liver, brain, kidney, bone, and lungs of African giant rats (AGRs) from three agro-ecological zones of Nigeria having different industrial activities was carried out using atomic absorption spectrophotometer. Twenty adult AGRs from cities in mangrove/freshwater swamp, rainforest, and woodland/tall grass savanna agro-ecological zones of Nigeria were used for this study. AGRs were euthanized, carefully dissected, and the brains, liver, lungs, bone, and kidneys were harvested, digested, and analyzed for concentrations of vanadium (V), lead (Pb), cadmium (Cd), zinc (Zn), selenium (Se), copper (Cu), and iron (Fe)...
August 14, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28808201/thalamic-paramagnetic-iron-by-t2-relaxometry-correlates-with-severity-of-multiple-sclerosis
#10
Eva Baranovicova, Ema Kantorova, Dagmar Kalenska, Lucia Lichardusova, Michal Bittsan-Sky, Dusan Dobrota
Iron can contribute to the pathogenesis and progression of multiple sclerosis (MS) due to its accumulation in the human brain. We focus on the thalamus as an information transmitter between various subcortical and cortical areas. Thalamic iron seems to follow different rules than iron in other deep gray matter structures and its relation to the clinical outcomes of MS is still indistinct. In our study, we investigated a connection between thalamic iron and patients' disability and course of the disease. The presence of paramagnetic substances in the tissues was tracked by T2* quantification...
July 13, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28806518/in-vivo-biosynthesized-zinc-and-iron-oxide-nanoclusters-for-high-spatiotemporal-dual-modality-bioimaging-of-alzheimer-s-disease
#11
Lanmei Lai, Xuerui Jiang, Shanying Han, Chunqiu Zhao, Tianyu Du, Fawad Ur Rehman, Youkun Zheng, Xiaoqi Li, Xiaoli Liu, Hui Jiang, Xuemei Wang
Alzheimer's disease is still incurable neurodegenerative, and lack of detection method with high sensitivity and specificity. In this study, by taking different month old Alzheimer's mice as models, we have explored the possibility of the target bioimaging of the diseased sites through the initial injection of zinc gluconate solution into Alzheimer's model mice post tail-vein, and then combination of the further injection of ferrous chloride (FeCl2) solution into the same Alzheimer's model mice post stomach...
August 14, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28803850/association-of-exposure-to-manganese-and-iron-with-striatal-and-thalamic-gaba-and-other-neurometabolites-neuroimaging-results-from-the-weldox-ii-study
#12
Swaantje Casjens, Urike Dydak, Shalmali Dharmadhikari, Anne Lotz, Martin Lehnert, Clara Quetscher, Christoph Stewig, Benjamin Glaubitz, Tobias Schmidt-Wilcke, David Edmondson, Chien-Lin Yeh, Tobias Weiss, Christoph van Thriel, Lennard Herrmann, Siegfried Muhlack, Dirk Woitalla, Michael Aschner, Thomas Brüning, Beate Pesch
OBJECTIVE: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. MATERIAL AND METHODS: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites...
August 10, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28800410/incident-risk-and-progression-of-cerebral-microbleeds-in-healthy-adults-a-multi-occasion-longitudinal-study
#13
Ana M Daugherty, Naftali Raz
Decline in cerebrovascular health complicates brain aging, and development of cerebral microbleeds (CMBs) is one of its prominent indicators. In a large sample of healthy adults (N = 251, age 18-78 years at baseline, 70% women), the contributions of chronological age and vascular health indicators to the risk of developing a CMB, as well as the change in CMB size and iron content, were examined in a prospective 8-year longitudinal study using susceptibility weighted imaging. Twenty-six persons (10.4%), most of whom were 40 years of age or older, had at least 1 CMB during the study...
July 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28797738/tissue-magnetic-susceptibility-mapping-as-a-marker-of-tau-pathology-in-alzheimer-s-disease
#14
J O'Callaghan, H Holmes, N Powell, J A Wells, O Ismail, I F Harrison, B Siow, R Johnson, Z Ahmed, A Fisher, S Meftah, M J O'Neill, T K Murray, E C Collins, K Shmueli, M F Lythgoe
Alzheimer's disease is connected to a number of other neurodegenerative conditions, known collectively as 'tauopathies', by the presence of aggregated tau protein in the brain. Neuroinflammation and oxidative stress in AD are associated with tau pathology and both the breakdown of axonal sheaths in white matter tracts and excess iron accumulation grey matter brain regions. Despite the identification of myelin and iron concentration as major sources of contrast in quantitative susceptibility maps of the brain, the sensitivity of this technique to tau pathology has yet to be explored...
August 4, 2017: NeuroImage
https://www.readbyqxmd.com/read/28792913/iron-in-neurodegenerative-disorders-being-in-the-wrong-place-at-the-wrong-time
#15
Sotirios Apostolakis, Anna-Maria Kypraiou
Brain iron deposits have been reported consistently in imaging and histologic examinations of patients with neurodegenerative disorders. While the origins of this finding have not been clarified yet, it is speculated that impaired iron homeostasis or deficient transport mechanisms result in the accumulation of this highly toxic metal ultimately leading to formation of reactive oxygen species and cell death. On the other hand, there are also those who support that iron is just an incidental finding, a by product of neuronal loss...
August 9, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28792609/egcg-attenuates-fe-iii-induced-conformational-transition-of-%C3%AE-synuclein-and-protects-as-pc12-cells-against-fe-iii-induced-death
#16
Juan Zhao, Lihui Xu, Qingnan Liang, Qing Sun, Congheng Chen, Yuan Zhang, Yu Ding, Ping Zhou
The fibrillation and aggregation of α-synuclein (AS), along with the conformational transition from random coil to β-sheet, are the critical steps in the development of Parkinson's disease (PD). It is acknowledged that iron accumulation in the brain may lead to the fibrillation of AS. However, (-)-epigallocatechin gallate (EGCG) can penetrate the blood-brain barrier, chelate metal ions and inhibit the fibrillation of amyloid proteins. Therefore, EGCG is warranted to be investigated for its potential to cure amyloid-related diseases...
August 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28781879/novel-pank2-mutation-in-the-first-greek-compound-heterozygote-patient-with-pantothenate-kinase-associated-neurodegeneration
#17
George P Paraskevas, Christos Yapijakis, Anastasia Bougea, Vasilios Constantinides, Mara Bourbouli, Eleftherios Stamboulis, Elisabeth Kapaki
Pantothenate-kinase-associated neurodegeneration is the most common autosomal recessive form of neurodegeneration with brain iron accumulation. Less than 100 mutations in PANK2 gene (20p13) are responsible for classic and atypical cases. We report here the first Greek case of atypical pantothenate-kinase-associated neurodegeneration, confirmed by molecular analysis that revealed two trans-acting mutations. Our findings highlight the possible role of rare variants contributing to disease risk and possibly to variable clinical phenotype...
2017: SAGE open medical case reports
https://www.readbyqxmd.com/read/28774878/the-actin-binding-protein-profilin-2-is-a-novel-regulator-of-iron-homeostasis
#18
Sara Luscieti, Bruno Galy, Lucia Gutierrez, Michael Reinke, Jorge Couso, Maya Shvartsman, Antonio Di Pascale, Walter Witke, Matthias W Hentze, Pietro Pilo Boyl, Mayka Sanchez
Cellular iron homeostasis is controlled by the iron regulatory proteins (IRPs) 1 and 2 that bind cis-regulatory iron-responsive elements (IRE) on target mRNAs. We identified the profilin2 (Pfn2) mRNA, which encodes an actin binding protein involved in endocytosis and neurotransmitters release, as a novel IRP-interacting transcript and studied its role in iron metabolism. Combination of EMSA experiments and bioinformatic analyses led to the identification of an atypical and conserved IRE in the 3' untranslated region of Pfn2 mRNA...
August 3, 2017: Blood
https://www.readbyqxmd.com/read/28771940/reduced-cerebral-white-matter-integrity-assessed-by-dti-in-cognitively-normal-h63d-hfe-polymorphism-carriers
#19
Mark D Meadowcroft, Jianli Wang, Carson J Purnell, Paul J Eslinger, Elizabeth B Neely, Qing X Yang, James R Connor
BACKGROUND AND PURPOSE: The H63D-HFE single nucleotide polymorphism (SNP) has been associated with brain iron dysregulation; however, the emergent role of this missense variant in brain structure and function has yet to be determined. Previous work has demonstrated that HFE SNP carriers have reduced white matter magnetic resonance imaging (MRI) proton relaxation rates. The mechanism by which white matter alterations perturb MRI relaxation is unknown as is how these metrics are related to myelin integrity...
August 3, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28769786/mild-inflammatory-profile-without-gliosis-in-the-c-rel-deficient-mouse-modeling-a-late-onset-parkinsonism
#20
Vanessa Porrini, Mariana Mota, Edoardo Parrella, Arianna Bellucci, Marina Benarese, Lara Faggi, Paolo Tonin, Pier F Spano, Marina Pizzi
The impact of neuroinflammation and microglial activation to Parkinson's disease (PD) progression is still debated. Post-mortem analysis of PD brains has shown that neuroinflammation and microgliosis are key features of end-stage disease. However, microglia neuroimaging studies and evaluation of cerebrospinal fluid (CSF) cytokines in PD patients at earlier stages do not support the occurrence of a pronounced neuroinflammatory process. PD animal models recapitulating the motor and non-motor features of the disease, and the slow and progressive neuropathology, can be of great advantage in understanding whether and how neuroinflammation associates with the onset of symptoms and neuronal loss...
2017: Frontiers in Aging Neuroscience
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