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Neuromolecular Medicine

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https://www.readbyqxmd.com/read/28718048/joint-effects-of-gwas-snps-in-coagulation-system-confer-risk-to-hypertensive-intracerebral-hemorrhage
#1
Yanyan Cao, Min Tian, Qin Fang, Zheng Wen, Wei Wang, Hu Ding, Dao Wen Wang
Recent genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with coagulation system, including hemostatic factors and hematological phenotypes. However, few articles described the relationships between these SNPs and the risk of hemorrhagic stroke. The aim of our study was to evaluate the roles of these SNPs as risk factors and survival predictors for hemorrhagic stroke. Thirteen SNPs from GWAS in coagulation system were genotyped in a Chinese Han population including 1000 patients with hemorrhagic stroke (intracerebral hemorrhage, ICH = 743; subarachnoid hemorrhage, SAH = 257) and 1044 population-based controls...
July 17, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28712006/an-inframe-trinucleotide-deletion-in-mtrr-exon-1-is-associated-with-the-risk-of-spina-bifida
#2
Jun Zhang, Xiao-Lu Dai, Gui-Cen Liu, Juan Wang, Xue-Yi Ren, Mu-Hua Jin, Nan-Nan Mi, Shu-Qin Wang
Maternal genetic variants of enzymes in folate-homocysteine metabolic network are significantly correlative with the risk of spina bifida. To survey the genetic causality, the genotypes of three women having spina bifida fetuses from two unrelated Chinese families were screened in candidate alleles. Polymerase chain reaction, capillary electrophoresis and Sanger sequencing were employed to recognize the allelic variation. A trinucleotide deletion (c.4_6delAGG) was identified in the first exon of MTRR. All the three women showed the novel clinical variation including one heterozygous and two homozygous...
July 15, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28695462/transgenic-mice-overexpressing-the-divalent-metal-transporter-1-exhibit-iron-accumulation-and-enhanced-parkin-expression-in-the-brain
#3
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/28689355/vitamin-d3-reverses-the-hippocampal-cytoskeleton-imbalance-but-not-memory-deficits-caused-by-ovariectomy-in-adult-wistar-rats
#4
Cassiana Siebert, Paula Pierozan, Janaina Kolling, Tiago Marcon Dos Santos, Matheus Coimbra Sebotaio, Eduardo Peil Marques, Helena Biasibetti, Aline Longoni, Fernanda Ferreira, Regina Pessoa-Pureur, Carlos Alexandre Netto, Angela T S Wyse
The objective of study was to investigate changes caused by ovariectomy (OVX) on aversive and non-aversive memories, as well as on cytoskeleton phosphorylating system and on vitamin D receptor (VDR) immunocontent in hippocampus. The neuroprotective role of vitamin D was also investigated. Ninety-day-old female Wistar rats were divided into four groups: SHAM, OVX, VITAMIN D and OVX + VITAMIN D; 30 days after the OVX, vitamin D supplementation (500 IU/kg), by gavage, for 30 days was started. Results showed that OVX impaired short-term and long-term recognition, and long-term aversive memories...
July 8, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28689354/functional-and-molecular-characterization-of-a-novel-traumatic-peripheral-nerve-muscle-injury-model
#5
Renate Wanner, Manuel Gey, Alireza Abaei, Daniela Warnecke, Luisa de Roy, Lutz Dürselen, Volker Rasche, Bernd Knöll
Traumatic injuries to human peripheral nerves are frequently associated with damage to nerve surrounding tissues including muscles and blood vessels. Currently, most rodent models of peripheral nerve injuries (e.g., facial or sciatic nerve) employ surgical nerve transection with scissors or scalpels. However, such an isolated surgical nerve injury only mildly damages neighboring tissues and weakly activates an immune response. In order to provide a rodent nerve injury model accounting for such nerve-associated tissue damage and immune cell activation, we developed a drop tower-based facial nerve trauma model in mice...
July 8, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28623611/deferiprone-rescues-behavioral-deficits-induced-by-mild-iron-exposure-in-a-mouse-model-of-alpha-synuclein-aggregation
#6
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/28620826/individual-amino-acid-supplementation-can-improve-energy-metabolism-and-decrease-ros-production-in-neuronal-cells-overexpressing-alpha-synuclein
#7
Vedad Delic, Jeddidiah W D Griffin, Sandra Zivkovic, Yumeng Zhang, Tam-Anh Phan, Henry Gong, Dale Chaput, Christian Reynes, Vinh B Dinh, Josean Cruz, Eni Cvitkovic, Devon Placides, Ernide Frederic, Hamed Mirzaei, Stanley M Stevens, Umesh Jinwal, Daniel C Lee, Patrick C Bradshaw
Parkinson's disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein accumulation and loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Increased levels of alpha-synuclein have been shown to result in loss of mitochondrial electron transport chain complex I activity leading to increased reactive oxygen species (ROS) production. WT alpha-synuclein was stably overexpressed in human BE(2)-M17 neuroblastoma cells resulting in increased levels of an alpha-synuclein multimer, but no increase in alpha-synuclein monomer levels...
June 15, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28612182/invaginating-presynaptic-terminals-in-neuromuscular-junctions-photoreceptor-terminals-and-other-synapses-of-animals
#8
REVIEW
Ronald S Petralia, Ya-Xian Wang, Mark P Mattson, Pamela J Yao
Typically, presynaptic terminals form a synapse directly on the surface of postsynaptic processes such as dendrite shafts and spines. However, some presynaptic terminals invaginate-entirely or partially-into postsynaptic processes. We survey these invaginating presynaptic terminals in all animals and describe several examples from the central nervous system, including giant fiber systems in invertebrates, and cup-shaped spines, electroreceptor synapses, and some specialized auditory and vestibular nerve terminals in vertebrates...
June 13, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28612181/low-density-lipoprotein-receptor-related-protein-1-lrp1-c4408r-mutant-promotes-amyloid-precursor-protein-app-%C3%AE-cleavage-in-vitro
#9
Huayan Hou, Ahsan Habib, Dan Zi, Kathy Tian, Jun Tian, Brian Giunta, Darrell Sawmiller, Jun Tan
Previous studies have demonstrated that the low-density lipoprotein receptor-related protein-1 (LRP1) plays conflicting roles in Alzheimer's disease (AD) pathogenesis, clearing β-amyloid (Aβ) from the brain while also enhancing APP endocytosis and resultant amyloidogenic processing. We have recently discovered that co-expression of mutant LRP1 C-terminal domain (LRP1-CT C4408R) with Swedish mutant amyloid precursor protein (APPswe) in Chinese hamster ovary (CHO) cells decreases Aβ production, while also increasing sAPPα and APP α-C-terminal fragment (α-CTF), compared with CHO cells expressing APPswe alone...
June 13, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28567584/rs3851179-polymorphism-at-5-to-the-picalm-gene-is-associated-with-alzheimer-and-parkinson-diseases-in-brazilian-population
#10
Cíntia Barros Santos-Rebouças, Andressa Pereira Gonçalves, Jussara Mendonça Dos Santos, Bianca Barbosa Abdala, Luciana Branco Motta, Jerson Laks, Margarete Borges de Borges, Ana Lúcia Zuma de Rosso, João Santos Pereira, Denise Hack Nicaretta, Márcia Mattos Gonçalves Pimentel
Alzheimer's (AD) and Parkinson's diseases (PD) share clinical and pathological features, suggesting that they could have common pathogenic mechanisms, as well as overlapping genetic modifiers. Here, we performed a case-control study in a Brazilian population to clarify whether the risk of AD and PD might be influenced by shared polymorphisms at PICALM (rs3851179), CR1 (rs6656401) and CLU (rs11136000) genes, which were previously identified as AD risk factors by genome-wide association studies. For this purpose, 174 late-onset AD patients, 166 PD patients and 176 matched controls were genotyped using TaqMan(®) assays...
May 31, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28536997/plxna3-variant-rs5945430-is-associated-with-severe-clinical-course-in-male-multiple-sclerosis-patients
#11
Moaz Qureshi, Mohamed Hatem, Raed Alroughani, Sindhu P Jacob, Rabeah Abbas Al-Temaimi
Multiple sclerosis (MS) exhibits sex bias in disease clinical course as male MS patients develop severe, progressive clinical course with accumulating disability. So far, no factors have been found associating with this sex bias in MS severity. We set out to determine the genetic factor contributing to MS male-specific progressive disease. This is an MS cross-sectional study involving 213 Kuwaiti MS patients recruited at Dasman Diabetes Institute. Exome sequencing was performed on 18 females and 8 male MS patients' genomic DNA...
May 23, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28536996/models-for-studying-myelination-demyelination-and-remyelination
#12
REVIEW
I Osorio-Querejeta, M Sáenz-Cuesta, M Muñoz-Culla, D Otaegui
One of the most widely studied demyelinating diseases is multiple sclerosis, which is characterised by the appearance of demyelinating plaques, followed by myelin regeneration. Nevertheless, with disease progression, remyelination tends to fail, increasing the characteristic neurodegeneration of the disease. It is essential to understand the mechanisms that operate in the processes of myelination, demyelination and remyelination to develop treatments that promote the production of new myelin, thereby protecting the central nervous system...
May 23, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28523591/assessment-of-the-neuroprotective-effects-of-arginine-rich-protamine-peptides-poly-arginine-peptides-r12-cyclic-r22-and-arginine-tryptophan-containing-peptides-following-in-vitro-excitotoxicity-and-or-permanent-middle-cerebral-artery-occlusion-in-rats
#13
Bruno P Meloni, Diego Milani, Jane L Cross, Vince W Clark, Adam B Edwards, Ryan S Anderton, David J Blacker, Neville W Knuckey
We have demonstrated that arginine-rich and poly-arginine peptides possess potent neuroprotective properties with arginine content and peptide positive charge being particularly critical for neuroprotective efficacy. In addition, the presence of other amino acids within arginine-rich peptides, as well as chemical modifications, peptide length and cell-penetrating properties also influence the level of neuroprotection. Against this background, we have examined the neuroprotective efficacy of arginine-rich protamine peptides, a cyclic (R12-c) poly-arginine peptide and a R22 poly-arginine peptide, as well as arginine peptides containing tryptophan or other amino acids (phenylalanine, tyrosine, glycine or leucine) in in vitro glutamic acid excitotoxicity and in vivo rat permanent middle cerebral artery occlusion models of stroke...
May 18, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/27592002/pro198leu-polymorphism-in-the-glutathione-peroxidase-1-gene-contributes-to-diabetic-peripheral-neuropathy-in-type-2-diabetes-patients
#14
Monika Buraczynska, Kinga Buraczynska, Michal Dragan, Andrzej Ksiazek
Glutathione peroxidase 1 (Gpx1) is an endogenous antioxidant enzyme. The T allele of the Pro198Leu polymorphism in the Gpx1 (rs1050450, 198C > T) gene is associated with reduced enzyme activity. The aim of this study was to evaluate the association between Pro198Leu polymorphism and risk of diabetic peripheral neuropathy (DPN). We examined 1244 T2DM patients and 730 healthy controls. In the patient group, 33 % had diabetic peripheral neuropathy. All subjects were genotyped for the Gpx1 Pro198Leu polymorphism by polymerase chain reaction and restriction analysis...
March 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/27488499/identification-of-novel-scirr69-interacting-proteins-during-er-stress-using-silac-immunoprecipitation-quantitative-proteomics-approach
#15
Yujian Chen, Yong Liu, Shide Lin, Shuguang Yang, Haiping Que, Shaojun Liu
Spinal cord injury and regeneration-related protein #69 (SCIRR69),also known as cAMP-responsive element-binding protein 3-like 2, belongs to the CREB/ATF family, some members of which play significant roles in ER stress. However, it is still not fully elucidated whether SCIRR69 involves in ER stress and its biochemical and functional roles during ER stress. In this study, we firstly treated fetal rat spinal cord neuron cells (SCN) and PC12 cells with ER stress activator thapsigargin (TG) or tunicamycin (TM) and then detected the expression pattern of SCIRR69 in response to ER stress at mRNA and protein levels using real-time PCR assay and immunoblotting...
March 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/27388466/increased-plasma-levels-of-select-deoxy-ceramide-and-ceramide-species-are-associated-with-increased-odds-of-diabetic-neuropathy-in-type-1-diabetes-a-pilot-study
#16
Samar M Hammad, Nathaniel L Baker, Jad M El Abiad, Stefanka D Spassieva, Jason S Pierce, Barbara Rembiesa, Jacek Bielawski, Maria F Lopes-Virella, Richard L Klein
Plasma deoxy-sphingoid bases are elevated in type 2 diabetes patients and correlate with the stage of diabetic distal sensorimotor polyneuropathy; however, associations between deoxy-sphingolipids (DSL) and neuropathy in type 1 diabetes have not been examined. The primary aim of this exploratory pilot study was to assess the associations between multiple sphingolipid species including DSL and free amino acids and the presence of symptomatic neuropathy in a DCCT/EDIC type 1 diabetes subcohort. Using mass spectroscopy, plasma levels of DSL and free amino acids in DCCT/EDIC type 1 diabetes participants (n = 80), with and without symptoms of neuropathy, were investigated...
March 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/27277280/potent-protection-against-mpp-induced-neurotoxicity-via-activating-transcription-factor-mef2d-by-a-novel-derivative-of-naturally-occurring-danshensu-tetramethylpyrazine
#17
Shengquan Hu, Liang Wang, Shinghung Mak, Zaijun Zhang, Daping Xu, Haitao Li, Yide Li, Yuanjia Hu, Simon Ming Yuen Lee, Yuqiang Wang, Yifan Han
Danshensu (DSS) and tetramethylpyrazine (TMP) are active ingredients of Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort that are widely used in oriental medicine. Structural combination of compounds with known biological activity may lead to the formation of a molecule with multiple properties or new function profile. In the current study, the neuroprotective effects of DT-010, a novel analogue in which TMP was coupled to DSS through an ester bond and two allyl groups at the carboxyl group, were evaluated in a cellular model of Parkinson's disease (PD)...
December 2016: Neuromolecular Medicine
https://www.readbyqxmd.com/read/27234618/plasma-amyloid-beta-1-42-and-dna-methylation-pattern-predict-accelerated-aging-in-young-subjects-with-down-syndrome
#18
Rima Obeid, Ulrich Hübner, Marion Bodis, Juergen Geisel
Gene methylation is an age-related dynamic process that influences diseases. Premature aging and disturbed methylation are components of Down syndrome (DS). We studied blood biomarkers and DNA methylation (DNAm) of three CpG sites (ASPA, ITGA2B, and PDE4C) in 60 elderly subjects (mean age = 68 years), 31 subjects with DS (12.1 years) and 44 controls (12.8 years). Plasma concentrations of amyloid beta (Aβ) 1-42 and biomarkers of methylation were measured in the young groups. Subjects with DS had significantly higher concentrations of plasma S-adenosylhomocysteine (SAH) and Aβ and reduced S-adenosylmethionine/SAH ratio compared with the controls...
December 2016: Neuromolecular Medicine
https://www.readbyqxmd.com/read/27230661/the-diversity-of-spine-synapses-in-animals
#19
REVIEW
Ronald S Petralia, Ya-Xian Wang, Mark P Mattson, Pamela J Yao
Here we examine the structure of the various types of spine synapses throughout the animal kingdom. Based on available evidence, we suggest that there are two major categories of spine synapses: invaginating and non-invaginating, with distributions that vary among different groups of animals. In the simplest living animals with definitive nerve cells and synapses, the cnidarians and ctenophores, most chemical synapses do not form spine synapses. But some cnidarians have invaginating spine synapses, especially in photoreceptor terminals of motile cnidarians with highly complex visual organs, and also in some mainly sessile cnidarians with rapid prey capture reflexes...
December 2016: Neuromolecular Medicine
https://www.readbyqxmd.com/read/27225841/metformin-protects-cells-from-mutant-huntingtin-toxicity-through-activation-of-ampk-and-modulation-of-mitochondrial-dynamics
#20
Jing Jin, Hao Gu, Nicole M Anders, Tianhua Ren, Mali Jiang, Michael Tao, Qi Peng, Michelle A Rudek, Wenzhen Duan
Huntington's disease (HD) is a devastating neurodegenerative disease caused by the pathological elongation of the CAG repeats in the huntingtin gene. Caloric restriction (CR) has been the most reproducible environmental intervention to improve health and prolong life span. We have demonstrated that CR delayed onset and slowed disease progression in a mouse model of HD. Metformin, an antidiabetic drug, mimics CR by acting on cell metabolism at multiple levels. Long-term administration of metformin improved health and life span in mice...
December 2016: Neuromolecular Medicine
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