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iron in the brain

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https://www.readbyqxmd.com/read/28731447/chromatin-bound-oxidized-%C3%AE-synuclein-causes-strand-breaks-in-neuronal-genomes-in-in-vitro-models-of-parkinson-s-disease
#1
Velmarini Vasquez, Joy Mitra, Pavana M Hegde, Arvind Pandey, Shiladitya Sengupta, Sankar Mitra, K S Rao, Muralidhar L Hegde
Alpha-synuclein (α-Syn) overexpression and misfolding/aggregation in degenerating dopaminergic neurons have long been implicated in Parkinson's disease (PD). The neurotoxicity of α-Syn is enhanced by iron (Fe) and other pro-oxidant metals, leading to generation of reactive oxygen species in PD brain. Although α-Syn is predominantly localized in presynaptic nerve terminals, a small fraction exists in neuronal nuclei. However, the functional and/or pathological role of nuclear α-Syn is unclear. Following up on our earlier report that α-Syn directly binds DNA in vitro, here we confirm the nuclear localization and chromatin association of α-Syn in neurons using proximity ligation and chromatin immunoprecipitation analysis...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731079/a-polymeric-temozolomide-nanocomposite-against-orthotopic-glioblastoma-xenograft-tumor-specific-homing-directed-by-nestin
#2
Suma Prabhu, Jayant Sastri Goda, Srinivas Mutalik, Bhabani Shankar Mohanty, Pradip Chaudhari, Sharada Rai, Nayanabhirama Udupa, Bola Sadashiva Satish Rao
The development of effective therapeutic strategies for glioblastoma faces challenges such as modulating the blood brain barrier (BBB) for drug influx and selectively targeting tumor cells. Nanocarrier drug delivery strategies are functionalized to enhance vascular permeability. We engineered superparamagnetic iron oxide nanoparticle (SPION) based polymeric nanocomposites (84.37 ± 12.37 nm / 101.56 ± 7.42 nm) embedding temozolomide (TMZ) targeted against glioblastoma by tagging an antibody against nestin, a stem cell marker, and transferrin / polysorbate-80 to permeate the BBB...
July 21, 2017: Nanoscale
https://www.readbyqxmd.com/read/28722486/neurotoxic-effects-of-subchronic-intratracheal-mn-nanoparticle-exposure-alone-and-in-combination-with-other-welding-fume-metals-in-rats
#3
Zsuzsanna Máté, Edina Horváth, András Papp, Krisztina Kovács, Etelka Tombácz, Dániel Nesztor, Tamás Szabó, Andrea Szabó, Edit Paulik
Manganese (Mn) is a toxic heavy metal exposing workers in various occupational settings and causing, among others, nervous system damage. Metal fumes of welding, a typical source of Mn exposure, contain a complex mixture of metal oxides partly in nanoparticle form. As toxic effects of complex substances cannot be sufficiently understood by examining its components separately, general toxicity and functional neurotoxicity of a main pathogenic welding fume metal, Mn, was examined alone and combined with iron (Fe) and chromium (Cr), also frequently found in fumes...
July 19, 2017: Inhalation Toxicology
https://www.readbyqxmd.com/read/28720846/physiological-stress-induced-corticosterone-increases-heme-uptake-via-klf4-hcp1-signaling-pathway-in-hippocampus-neurons
#4
Hongxia Li, Caixia Zhang, Hui Shen, Zhilei Shen, Lusha Wu, Fengfeng Mo, Min Li
Iron overload has attracted much attention because of its adverse effect in increasing the risk of developing several neurodegenerative disorders. Under various pathologic conditions, a lot of heme are released. The aggregation of heme is more neurotoxic than that of iron released from the heme breakdown. Our previous studies demonstrated that psychological stress (PS) is a risk factor of cerebral iron metabolism disorders, thus causing iron accumulation in rat brains. In the present study, we found PS could increase heme uptake via heme carrier protein 1 (HCP1) in rat brains...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716262/new-genetic-causes-for-complex-hereditary-spastic-paraplegia
#5
Paulo Victor Sgobbi de Souza, Thiago Bortholin, Renan Braido Dias, Marco Antônio Troccoli Chieia, Stênio Burlin, Fernando George Monteiro Naylor, Wladimir Bocca Vieira de Rezende Pinto, Acary Souza Bulle Oliveira
INTRODUCTION: Hereditary Spastic Paraplegia (HSP) represents a complex and heterogeneous group of rare neurodegenerative disorders that share a common clinical feature of weakness and lower limb spasticity that can occur alone or in combination with a constellation of other neurological or systemic signs and symptoms. Although the core clinical feature of weakness and lower limb spasticity is virtually universal, the genetic heterogeneity is almost uncountable with more than 70 genetic forms described so far...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28715425/elimination-of-huntingtin-in-the-adult-mouse-leads-to-progressive-behavioral-deficits-bilateral-thalamic-calcification-and-altered-brain-iron-homeostasis
#6
Paula Dietrich, Irudayam Maria Johnson, Shanta Alli, Ioannis Dragatsis
Huntington's Disease (HD) is an autosomal dominant progressive neurodegenerative disorder characterized by cognitive, behavioral and motor dysfunctions. HD is caused by a CAG repeat expansion in exon 1 of the HD gene that is translated into an expanded polyglutamine tract in the encoded protein, huntingtin (HTT). While the most significant neuropathology of HD occurs in the striatum, other brain regions are also affected and play an important role in HD pathology. To date there is no cure for HD, and recently strategies aiming at silencing HTT expression have been initiated as possible therapeutics for HD...
July 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28711740/early-manifestations-of-epileptic-encephalopathy-brain-atrophy-and-elevation-of-serum-neuron-specific-enolase-in-a-boy-with-beta-propeller-protein-associated-neurodegeneration
#7
Kyoko Takano, Kazuya Goto, Mitsuo Motobayashi, Keiko Wakui, Rie Kawamura, Tomomi Yamaguchi, Yoshimitsu Fukushima, Tomoki Kosho
Mutations in WDR45 are responsible for beta-propeller protein-associated neurodegeneration (BPAN), which is an X-linked form of neurodegeneration with brain iron accumulation. BPAN mainly affects females and is characterized by seizures and developmental delay or intellectual disability until adolescence or early adulthood, followed by severe dystonia, parkinsonism, and progressive dementia. However, rare male patients have recently been reported with hemizygous germline mutations in WDR45 and severe clinical manifestations, such as epileptic encephalopathies...
July 12, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28710084/neuroprotective-strategies-following-intraparenchymal-hemorrhage
#8
REVIEW
Robin Moshe Babadjouni, Ryan E Radwanski, Brian P Walcott, Arati Patel, Ramon Durazo, Drew M Hodis, Benjamin A Emanuel, William J Mack
Intracerebral hemorrhage and, more specifically, intraparenchymal hemorrhage, are devastating disease processes with poor clinical outcomes. Primary injury to the brain results from initial hematoma expansion while secondary hemorrhagic injury occurs from blood-derived products such as hemoglobin, heme, iron, and coagulation factors that overwhelm the brains natural defenses. Novel neuroprotective treatments have emerged that target primary and secondary mechanisms of injury. Nonetheless, translational application of neuroprotectants from preclinical to clinical studies has yet to show beneficial clinical outcomes...
July 14, 2017: Journal of Neurointerventional Surgery
https://www.readbyqxmd.com/read/28700687/secretory-carrier-membrane-protein-5-is-an-autophagy-inhibitor-that-promotes-the-secretion-of-%C3%AE-synuclein-via-exosome
#9
Yi Yang, Meiling Qin, Puhua Bao, Wangchao Xu, Jin Xu
Autophagy-lysosomal pathway is a cellular protective system to remove aggregated proteins and damaged organelles. Meanwhile, exosome secretion has emerged as a mode to selectively clear the neurotoxic proteins, such as α-synuclein. Mounting evidence suggests that these two cellular processes are coordinated to facilitate the clearance of toxic cellular waste; however the regulators for the transition between these two processes are unclear. Here we show that SCAMP5, a secretory carrier membrane protein significantly induced in the brains of Huntington's disease patients, is quickly and transiently induced by protein stress and autophagic stimulation, and is regulated by the master autophagy transcriptional regulator TFEB...
2017: PloS One
https://www.readbyqxmd.com/read/28695462/transgenic-mice-overexpressing-the-divalent-metal-transporter-1-exhibit-iron-accumulation-and-enhanced-parkin-expression-in-the-brain
#10
Cheng-Wu Zhang, Yee Kit Tai, Bing-Han Chai, Katherine C M Chew, Eng-Tat Ang, Fai Tsang, Bryce W Q Tan, Eugenia T E Hong, Abu Bakar Ali Asad, Kai-Hsiang Chuang, Kah-Leong Lim, Tuck Wah Soong
Exposure to divalent metals such as iron and manganese is thought to increase the risk for Parkinson's disease (PD). Under normal circumstances, cellular iron and manganese uptake is regulated by the divalent metal transporter 1 (DMT1). Accordingly, alterations in DMT1 levels may underlie the abnormal accumulation of metal ions and thereby disease pathogenesis. Here, we have generated transgenic mice overexpressing DMT1 under the direction of a mouse prion promoter and demonstrated its robust expression in several regions of the brain...
July 10, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28695311/aberrant-paramagnetic-signals-outside-the-tumor-volume-on-routine-surveillance-mri-of-brain-tumor-patients
#11
Shlomit Yust-Katz, Edna Inbar, Natalia Michaeli, Dror Limon, Tali Siegal
Late complications of cerebral radiation therapy (RT) involve vascular injury with acquired cavernous malformation, telangiectasias and damage to vascular walls which are well recognized in children. Its incidence in adults is unknown. Blood products and iron deposition that accompany vascular injury create paramagnetic effects on MRI. This study retrospectively investigated the frequency of paramagnetic lesions on routine surveillance MRI of adult brain tumor patients. MRI studies of 115 brain tumor patients were reviewed...
July 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28694463/contrast-enhanced-mr-microscopy-of-amyloid-plaques-in-five-mouse-models-of-amyloidosis-and-in-human-alzheimer-s-disease-brains
#12
Clémence Dudeffant, Matthias Vandesquille, Kelly Herbert, Clément M Garin, Sandro Alves, Véronique Blanchard, Emmanuel E Comoy, Fanny Petit, Marc Dhenain
Gadolinium (Gd)-stained MRI is based on Gd contrast agent (CA) administration into the brain parenchyma. The strong signal increase induced by Gd CA can be converted into resolution enhancement to record microscopic MR images. Moreover, inhomogeneous distribution of the Gd CA in the brain improves the contrast between different tissues and provides new contrasts in MR images. Gd-stained MRI detects amyloid plaques, one of the microscopic lesions of Alzheimer's disease (AD), in APPSL/PS1M146L mice or in primates...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692911/relationship-between-heavy-metal-accumulation-and-morphometric-parameters-in-european-hare-lepus-europaeus-inhabiting-various-types-of-landscapes-in-southern-poland
#13
Marek Wajdzik, Wiktor Halecki, Konrad Kalarus, Michał Gąsiorek, Marek Pająk
To evaluate the influence of hazardous substances in the environment, studies of pollutant accumulation in wild living animals are needed. Studies dealing with heavy metal contamination in mammals usually focus on a single organ. We investigated accumulation of heavy metals as well as iron in European hare (Lepus europaeus) living in southern Poland, Małopolska Province. Hares were captured during the hunting season. We tested metal accumulation in 14 organs and tissues using 35 individuals with known body weight and sex inhabiting agricultural, industrial and other types of landscapes...
July 7, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28692648/zebrafish-slc30a10-deficiency-revealed-a-novel-compensatory-mechanism-of-atp2c1-in-maintaining-manganese-homeostasis
#14
Zhidan Xia, Jiayu Wei, Yingniang Li, Jia Wang, Wenwen Li, Kai Wang, Xiaoli Hong, Lu Zhao, Caiyong Chen, Junxia Min, Fudi Wang
Recent studies found that mutations in the human SLC30A10 gene, which encodes a manganese (Mn) efflux transporter, are associated with hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMDPC). However, the relationship between Mn metabolism and HMDPC is poorly understood, and no specific treatments are available for this disorder. Here, we generated two zebrafish slc30a10 mutant lines using the CRISPR/Cas9 system. Compared to wild-type animals, mutant adult animals developed significantly higher systemic Mn levels, and Mn accumulated in the brain and liver of mutant embryos in response to exogenous Mn...
July 10, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28689117/development-of-non-pyrogenic-magnetosome-minerals-coated-with-poly-l-lysine-leading-to-full-disappearance-of-intracranial-u87-luc-glioblastoma-in-100-of-treated-mice-using-magnetic-hyperthermia
#15
Edouard Alphandéry, Ahmed Idbaih, Clovis Adam, Jean-Yves Delattre, Charlotte Schmitt, François Guyot, Imène Chebbi
Magnetic hyperthermia was reported to increase the survival of patients with recurrent glioblastoma by 7 months. This promising result may potentially be further improved by using iron oxide nanoparticles, called magnetosomes, which are synthesized by magnetotactic bacteria, extracted from these bacteria, purified to remove most endotoxins and organic material, and then coated with poly-l-lysine to yield a stable and non-pyrogenic nanoparticle suspension. Due to their ferrimagnetic behavior, high crystallinity and chain arrangement, these magnetosomes coated with poly-l-lysine (M-PLL) are characterized by a higher heating power than their chemically synthesized counterparts currently used in clinical trials...
June 21, 2017: Biomaterials
https://www.readbyqxmd.com/read/28684912/the-effects-of-grafted-mesenchymal-stem-cells-labeled-with-iron-oxide-or-cobalt-zinc-iron-nanoparticles-on-the-biological-macromolecules-of-rat-brain-tissue-extracts
#16
Bozena Novotna, Vit Herynek, Pavel Rossner, Karolina Turnovcova, Pavla Jendelova
INTRODUCTION: Rat mesenchymal stem cells (rMSCs) labeled with 1) poly-l-lysine-coated superparamagnetic iron oxide nanoparticles or 2) silica-coated cobalt-zinc-iron nanoparticles were implanted into the left brain hemisphere of rats, to assess their effects on the levels of oxidative damage to biological macromolecules in brain tissue. METHODS: Controls were implanted with unlabeled rMSCs. Animals were sacrificed 24 hours or 4 weeks after the treatment, and the implantation site along with the surrounding tissue was isolated from the brain...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28680084/a-variation-in-pank2-gene-is-causing-pantothenate-kinase-associated-neurodegeneration-in-a-family-from-jammu-and-kashmir-india
#17
Arshia Angural, Inderpal Singh, Ankit Mahajan, Pranav Pandoh, Manoj K Dhar, Sanjana Kaul, Vijeshwar Verma, Ekta Rai, Sushil Razdan, Kamal Kishore Pandita, Swarkar Sharma
Pantothenate kinase-associated neurodegeneration is a rare hereditary neurodegenerative disorder associated with nucleotide variation(s) in mitochondrial human Pantothenate kinase 2 (hPanK2) protein encoding PANK2 gene, and is characterized by symptoms of extra-pyramidal dysfunction and accumulation of non-heme iron predominantly in the basal ganglia of the brain. In this study, we describe a familial case of PKAN from the State of Jammu and Kashmir (J&K), India based on the clinical findings and genetic screening of two affected siblings born to consanguineous normal parents...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28675230/one-pot-synthesis-of-nanochain-particles-for-targeting-brain-tumors
#18
V S Perera, G Covarrubias, M Lorkowski, P Atukorale, A Rao, S Raghunathan, R Gopalakrishnan, B O Erokwu, Y Liu, D Dixit, S M Brady-Kalnay, D Wilson, C Flask, J Rich, P M Peiris, E Karathanasis
To synthesize multi-component nanochains, we developed a simple 'one-pot' synthesis, which exhibited high yield and consistency. The nanochains particles consist of parent nanospheres chemically linked into a higher-order, chain-like assembly. The one-pot synthesis is based on the addition of two types of parent nanospheres in terms of their surface chemical functionality (e.g., decorated with PEG-NH2 or PEG-COOH). By reacting the two types of parent nanospheres at a specific ratio (∼2 : 1) for a short period of time (∼30 min) under rigorous stirring, nanochains were formed...
July 13, 2017: Nanoscale
https://www.readbyqxmd.com/read/28675187/the-iron-paradox-a-case-of-acaeruloplasminaemia
#19
J Williamson, J Holt
Acaeruloplasminaemia is a rare neurodegenerative disorder in which dysfunction of the caeruloplasmin gene results in brain iron accumulation alongside systemic iron overload. We discuss the case of a 53-year-old male who presented to neurology with a 4-year history of progressive neuropsychiatric symptoms and was eventually diagnosed with this condition. We discuss the characteristic clinical features and supporting laboratory and radiological findings as well as clinical pointers to help differentiate it from other conditions which might cause diagnostic confusion...
June 2017: Journal of the Royal College of Physicians of Edinburgh
https://www.readbyqxmd.com/read/28671115/iron-concentration-in-deep-gray-matter-structures-is-associated-with-worse-visual%C3%A2-memory-performance-in-healthy-young-adults
#20
Gergely Darnai, Szilvia Anett Nagy, Réka Horváth, Péter Ács, Gábor Perlaki, Gergely Orsi, Norbert Kovács, Anna Altbäcker, Enikő Plózer, Dalma Tényi, Rita Weintraut, Attila Schwarcz, Flóra John, Eszter Varga, Tamás Bereczkei, Zsófia Clemens, Sámuel Komoly, József Janszky
Abnormally high deposition of iron can contribute to neurodegenerative disorders with cognitive impairment. Since previous studies investigating cognition-brain iron accumulation relationships focused on elderly people, our aim was to explore the association between iron concentration in subcortical nuclei and two types of memory performances in a healthy young population. Gender difference was found only in the globus pallidus. Our results showed that iron load characterized by R2* value on the MRI in the caudate and putamen was related to visual memory, while verbal memory was unrelated to iron concentration...
June 27, 2017: Journal of Alzheimer's Disease: JAD
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