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https://www.readbyqxmd.com/read/28636371/iron-oxidation-and-core-formation-in-recombinant-heteropolymeric-human-ferritins
#1
Matthew R Mehlenbacher, Maura Poli, Paolo Arosio, Paolo Santambrogio, Sonia Levi, N Dennis Chasteen, Fadi Bou-Abdallah
In animals, the iron storage and detoxification protein, ferritin, is composed of two functionally and genetically distinct subunit types, H (Heavy) and L (Light), which co-assemble in various ratios with tissue specific distributions to form shell-like protein structures of 24 subunits within which a mineralized iron core is stored. The H-subunit possesses a ferroxidase center (FC) which catalyzes Fe(II) oxidation whereas the L-subunit does not. To assess the role of the L-subunit in iron oxidation and core formation, two human recombinant heteropolymeric ferritins, designated H-rich and L-rich with ratios of ~ 20H:4L and ~ 22L:2H, respectively, were employed and compared to the human homopolymeric H-subunit ferritin (HuHF)...
June 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28632387/poly-trehalose-nanoparticle-prevents-amyloid-aggregation-and-suppress-polyglutamine-aggregation-in-huntington-s-disease-model-mouse
#2
Koushik Debnath, Nibedita Pradhan, Brijesh Kumar Singh, Nihar R Jana, Nikhil R Jana
Prevention and therapeutic strategy of various neurodegenerative disease focus on inhibiting protein fibrillation, clearing of aggregated protein plaques from brain and lowering of protein aggregate-induced toxicity. We have designed poly(trehalose) nanoparticle that can inhibit amyloid/polyglutamine aggregation under extra-/intra-cellular condition, reduce such aggregation-derived cytotoxicity and prevents polyglutamine aggregation in Huntington's disease (HD) model mouse brain. Nanoparticle has 20-30 nm hydrodynamic size, composed of 6 nm iron oxide core and zwitterionic polymer shell with covalently linked trehalose of ~5-12 wt %...
June 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28626420/restless-legs-syndrome-from-pathophysiology-to-clinical-diagnosis-and-management
#3
REVIEW
Shiyi Guo, Jinsha Huang, Haiyang Jiang, Chao Han, Jie Li, Xiaoyun Xu, Guoxin Zhang, Zhicheng Lin, Nian Xiong, Tao Wang
Restless legs syndrome (RLS), a common neurological sensorimotor disorder in western countries, has gained more and more attention in Asian countries. The prevalence of RLS is higher in older people and females. RLS is most commonly related to iron deficiency, pregnancy and uremia. The RLS symptoms show a significant circadian rhythm and a close relationship to periodic limb movements (PLMs) in clinical observations, while the pathophysiological pathways are still unknown. The diagnostic criteria have been revised in 2012 to improve the validity of RLS diagnosis...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28623639/anemia-after-continuous-flow-left-ventricular-assist-device-implantation-characteristics-and-implications
#4
Javier Amione-Guerra, Ana S Cruz-Solbes, Arvind Bhimaraj, Barry H Trachtenberg, Sai R Pingali, Jerry D Estep, Myung H Park, Ashrith Guha
BACKGROUND: Anemia is common in patients with heart failure and is associated with adverse outcomes. Management of anemia in CF-LVAD patients is not well studied. Our purpose is to characterize and identify the etiology of anemia in CF-LVAD patients. Secondary objectives are to describe the effect of CF-LVAD on pre-existing anemia and assess its impact after CF-LVAD support. METHODS: Cross-sectional study from January to July 2015 of ambulatory patients supported with a CF-LVAD for at least 6-months that presented with hemoglobin <12 g/dL and no recent gastrointestinal bleeding...
June 14, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28623611/deferiprone-rescues-behavioral-deficits-induced-by-mild-iron-exposure-in-a-mouse-model-of-alpha-synuclein-aggregation
#5
Eleonora Carboni, Lars Tatenhorst, Lars Tönges, Elisabeth Barski, Vivian Dambeck, Mathias Bähr, Paul Lingor
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, and its causes remain unknown. A major hallmark of the disease is the increasing presence of aggregated alpha-synuclein (aSyn). Furthermore, there is a solid consensus on iron (Fe) accumulation in several regions of PD brains during disease progression. In our study, we focused on the interaction of Fe and aggregating aSyn in vivo in a transgenic mouse model overexpressing human aSyn bearing the A53T mutation (prnp.aSyn.A53T). We utilized a neonatal iron-feeding model to exacerbate the motor phenotype of the transgenic mouse model...
June 16, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28622777/-iron-and-neurodevelopment
#6
L Vallée
In the central nervous system, iron is a cofactor of many metabolic processes and synthesis of aminergic neurotransmitters. Iron plays an major function on brain development from the prenatal period to teenage years. The blood-brain barrier modulates concentration of iron in the brain. In case of iron deficiency in the child, the negative impact on the myelinogenesis and synaptogenesis are well proven, with negative effects on psychomotor and cognitive functions. Iron supplementation has a beneficial effect, even if there is no anemia...
May 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28621205/neurocognitive-dysfunction-in-children-with-%C3%AE-thalassemia-major-psychometric-neurophysiologic-and-radiologic-evaluation
#7
M S Elalfy, R H Aly, H Azzam, K Aboelftouh, R H Shatla, M Tarif, M Abdatty, R M Elsayed
OBJECTIVE: To evaluate the impact of iron chelating drugs and serum ferritin on the neurocognitive functions of patients with β thalassemia major (β-TM), using psychometric, neurophysiologic and radiologic tests. METHODS: Eighty children with β-TM were enrolled into the study and were compared to 40 healthy controls. All participants were evaluated by measuring serum ferritin, neurocognitive assessment by Benton Visual Retention Test, Wechsler Intelligence Scale for Children, Wisconsin Card Sort Test, P300 and magnetic resonance spectroscopy (MRS)...
June 16, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28620665/influence-of-iron-metabolism-on-manganese-transport-and-toxicity
#8
REVIEW
Qi Ye, Jo Eun Park, Kuljeet Gugnani, Swati Betharia, Alejandro Pino-Figueroa, Jonghan Kim
Although manganese (Mn) is critical for the proper functioning of various metabolic enzymes and cofactors, excess Mn in the brain causes neurotoxicity. While the exact transport mechanism of Mn has not been fully understood, several importers and exporters for Mn have been identified over the past decade. In addition to Mn-specific transporters, it has been demonstrated that iron transporters can mediate Mn transport in the brain and peripheral tissues. However, while the expression of iron transporters is regulated by body iron stores, whether or not disorders of iron metabolism modify Mn homeostasis has not been systematically discussed...
June 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28619513/myricetin-ameliorates-scopolamine-induced-memory-impairment-in-mice-via-inhibiting-acetylcholinesterase-and-down-regulating-brain-iron
#9
Beiyun Wang, Yuan Zhong, Chengjie Gao, Jingbo Li
The aim of our study was to investigate to investigate the effect of myricetin on Alzheimer's disease (AD) and its underlying mechanisms. In our study, Myricetin effectively attenuated Fe(2+)-induced cell death in SH-SY5Y cells in vitro. In a mouse model of AD, myricetin treatment significantly reversed scopolamine-induced cognitive deficits deriving from a novel action of inhibiting acetylcholinesterase (AChE) and down-regulating brain iron. Furthermore, Myricetin treatment reduced oxidative damage and increased antioxidant enzymes activity in mice...
June 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28618115/iron-sulfur-glutaredoxin-2-protects-oligodendrocytes-against-damage-induced-by-nitric-oxide-release-from-activated-microglia
#10
Klaudia Lepka, Katrin Volbracht, Eckhard Bill, Reiner Schneider, Natalia Rios, Thomas Hildebrandt, Jens Ingwersen, Timur Prozorovski, Christopher Horst Lillig, Jack van Horssen, Lawrence Steinman, Hans-Peter Hartung, Rafael Radi, Arne Holmgren, Orhan Aktas, Carsten Berndt
Demyelinated brain lesions, a hallmark of autoimmune neuroinflammatory diseases like multiple sclerosis, result from oligodendroglial cell damage. Activated microglia are considered a major source of nitric oxide and subsequent peroxynitrite-mediated damage of myelin. Here, we provide biochemical and biophysical evidence that the oxidoreductase glutaredoxin 2 inhibits peroxynitrite formation by transforming nitric oxide into dinitrosyl-diglutathionyl-iron-complexes. Glutaredoxin 2 levels influence both survival rates of primary oligodendrocyte progenitor cells and preservation of myelin structure in cerebellar organotypic slice cultures challenged with activated microglia or nitric oxide donors...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28618066/assessment-of-ferritin-content-in-multiple-sclerosis-brains-using-temperature-induced-r-2-changes
#11
Christoph Birkl, Daniele Carassiti, Fariha Hussain, Christian Langkammer, Christian Enzinger, Franz Fazekas, Klaus Schmierer, Stefan Ropele
PURPOSE: Current MRI techniques cannot reliably assess iron content in white matter due to the confounding diamagnetic effect of myelin. The purpose of this study was to validate with histology a novel iron mapping technique that uses the temperature dependency of the paramagnetic susceptibility in multiple sclerosis (MS) brains, where white matter has been reported to show significant variations in iron content. METHODS: We investigated post mortem brain tissue from three MS patients and one control subject...
June 15, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28616842/characterization-of-magneto-endosymbionts-as-mri-cell-labeling-and-tracking-agents
#12
Kimberly D Brewer, Ryan Spitler, Kayla R Lee, Andrea C Chan, Joyce C Barrozo, Abdul Wakeel, Chandler S Foote, Steven Machtaler, James Rioux, Juergen K Willmann, Papia Chakraborty, Bradley W Rice, Christopher H Contag, Caleb B Bell, Brian K Rutt
PURPOSE: Magneto-endosymbionts (MEs) show promise as living magnetic resonance imaging (MRI) contrast agents for in vivo cell tracking. Here we characterize the biomedical imaging properties of ME contrast agents, in vitro and in vivo. PROCEDURES: By adapting and engineering magnetotactic bacteria to the intracellular niche, we are creating magneto-endosymbionts (MEs) that offer advantages relative to passive iron-based contrast agents (superparamagnetic iron oxides, SPIOs) for cell tracking...
June 14, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28612835/coexisting-variants-in-ostm1-and-maneal-cause-a-complex-neurodegenerative-disorder-with-nbia-like-brain-abnormalities
#13
Diran Herebian, Bader Alhaddad, Annette Seibt, Thomas Schwarzmayr, Katharina Danhauser, Dirk Klee, Stefani Harmsen, Thomas Meitinger, Tim M Strom, Ansgar Schulz, Ertan Mayatepek, Tobias B Haack, Felix Distelmaier
Coexistence of different hereditary diseases is a known phenomenon in populations with a high consanguinity rate. The resulting clinical phenotypes are extremely challenging for physicians involved in the care of these patients. Here we describe a 6-year-old boy with co-occurrence of a homozygous splice defect in OSTM1, causing infantile malignant osteopetrosis, and a loss-of-function variant in MANEAL, which has not been associated with human disease so far. The child suffered from severe infantile-onset neurodegeneration that could not be stopped by bone marrow transplantation...
June 14, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28610994/manganese-induced-sex-specific-gut-microbiome-perturbations-in-c57bl-6-mice
#14
Liang Chi, Bei Gao, Xiaoming Bian, Pengcheng Tu, Hongyu Ru, Kun Lu
Overexposure to manganese (Mn) leads to toxic effects, such as promoting the development of Parkinson's-like neurological disorders. The gut microbiome is deeply involved in immune development, host metabolism, and xenobiotics biotransformation, and significantly influences central nervous system (CNS) via the gut-brain axis, i.e. the biochemical signaling between the gastrointestinal tract and the CNS. However, it remains unclear whether Mn can affect the gut microbiome and its metabolic functions, particularly those linked to neurotoxicity...
June 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28606049/the-blood-brain-barrier-and-its-role-in-alzheimer-s-therapy-an-overview
#15
Satya Lavanya Jakki, V Senthil, Venkata Ramesh Yasam, Mjn Chandrasekar, C Vijayaraghavan
Alzheimer`s disease (AD) is the most frequent age related neurodegenerative disorder. It represents 70% of all dementia. Millions of people have been affected by AD worldwide. It is a complex illness characterized pathologically by accumulation of protein aggregates of amyloid and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein. AD requires drugs that can circumvent the blood-brain barrier (BBB) which is not a simple physical barrier between blood and brain, but acts as an iron curtain, allowing only selective molecules to enter the brain...
June 12, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28601374/quantitative-susceptibility-mapping-qsm-and-r2-in-the-human-brain-at-3t-evaluation-of-intra-scanner-repeatability
#16
Xiang Feng, Andreas Deistung, Jürgen R Reichenbach
Quantitative susceptibility mapping (QSM) and the effective transverse relaxation rate (R2*) can be used to monitor iron and myelin content in brain tissue, which are both subject to changes in many neurological diseases but also during healthy aging. In this study, we quantitatively assessed the repeatability of QSM and R2* by applying four independent scans in eight young healthy, female subjects on a 3T MRI scanner. Since QSM does not yield absolute values for bulk magnetic susceptibilities, we additionally investigated the influence of the choice of a reference brain region for susceptibility by computing susceptibility differences with respect to five different brain structures (whole brain, frontal white matter (fWM), internal capsule (IC), cerebrospinal fluid (CSF) in the lateral ventricle, cortical gray matter (cGM))...
June 7, 2017: Zeitschrift Für Medizinische Physik
https://www.readbyqxmd.com/read/28599322/monoamine-oxidase-a-upregulated-by-chronic-intermittent-hypoxia-activates-indoleamine-2-3-dioxygenase-and-neurodegeneration
#17
Chun-Sing Lam, Jing-Jie Li, George Lim Tipoe, Moussa B H Youdim, Man-Lung Fung
Co-morbid depression is prevalent in patients with obstructive sleep apnea. Here we report that monoamine oxidase A (MAO-A) plays pathogenic roles in the comorbidity. We found that chronic intermittent hypoxia significantly increased the MAO-A expression in the rat hippocampus and markedly decreased the dendritic length and spine density in the pyramidal neurons with less pre- and post-synaptic proteins. The MAO-A upregulation resulted in increased 5-hydroxyindoleacetic acid/serotonin ratio, oxidative stress, leading to NF-κB activation, inflammation and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28598844/combustion-derived-nanoparticles-in-key-brain-target-cells-and-organelles-in-young-urbanites-culprit-hidden-in-plain-sight-in-alzheimer-s-disease-development
#18
Angélica González-Maciel, Rafael Reynoso-Robles, Ricardo Torres-Jardón, Partha S Mukherjee, Lilian Calderón-Garcidueñas
Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer's disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF) Aβ1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson's disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites' brains...
June 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28596835/chronic-diazepam-administration-increases-the-expression-of-lcn2-in-the-cns
#19
Tomonori Furukawa, Shuji Shimoyama, Yasuo Miki, Yoshikazu Nikaido, Kohei Koga, Kazuhiko Nakamura, Koichi Wakabayashi, Shinya Ueno
Benzodiazepines (BZDs), which bind with high affinity to gamma-aminobutyric acid type A receptors (GABAA-Rs) and potentiate the effects of GABA, are widely prescribed for anxiety, insomnia, epileptic discharge, and as anticonvulsants. The long-term use of BZDs is limited due to adverse effects such as tolerance, dependence, withdrawal effects, and impairments in cognition and learning. Additionally, clinical reports have shown that chronic BZD treatment increases the risk of Alzheimer's disease. Unusual GABAA-R subunit expression and GABAA-R phosphorylation are induced by chronic BZD use...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28595912/the-effect-of-manganese-exposure-in-atp13a2-deficient-mice
#20
Sheila M Fleming, Nicholas A Santiago, Elizabeth J Mullin, Shanta Pamphile, Swagata Karkare, Andrew Lemkuhl, Osunde R Ekhator, Stephen C Linn, John G Holden, Diana S Aga, Jerome A Roth, Benjamin Liou, Ying Sun, Gary E Shull, Patrick J Schultheis
Loss of function mutations in the P5-ATPase ATP13A2 are associated with Kufor-Rakeb Syndrome and Neuronal Ceroid Lipofuscinosis. While the function of ATP13A2 is unclear, in vitro studies suggest it is a lysosomal protein that interacts with the metals manganese (Mn) and zinc and the presynaptic protein alpha-synuclein. Loss of ATP13A2 function in mice causes sensorimotor deficits, enhanced autofluorescent storage material, and accumulation of alpha-synuclein. The present study sought to determine the effect of Mn administration on these same outcomes in ATP13A2-deficient mice...
June 6, 2017: Neurotoxicology
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