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apoE spinal cord

Carrie J Finno, Matthew H Bordbari, Stephanie J Valberg, David Lee, Josi Herron, Kelly Hines, Tamer Monsour, Erica Scott, Danika L Bannasch, James Mickelson, Libin Xu
Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord...
October 14, 2016: Free Radical Biology & Medicine
Dina Safina, Frederik Schlitt, Ramona Romeo, Thorsten Pflanzner, Claus U Pietrzik, Vasanthy Narayanaswami, Frank Edenhofer, Andreas Faissner
The LDL family of receptors and its member low-density lipoprotein receptor-related protein 1 (LRP1) have classically been associated with a modulation of lipoprotein metabolism. Current studies, however, indicate diverse functions for this receptor in various aspects of cellular activities, including cell proliferation, migration, differentiation, and survival. LRP1 is essential for normal neuronal function in the adult CNS, whereas the role of LRP1 in development remained unclear. Previously, we have observed an upregulation of LewisX (LeX) glycosylated LRP1 in the stem cells of the developing cortex and demonstrated its importance for oligodendrocyte differentiation...
August 2016: Glia
Zhen Gu, Fengqiao Li, Yi Ping Zhang, Lisa B E Shields, Xiaoling Hu, Yiyan Zheng, Panpan Yu, Yongjie Zhang, Jun Cai, Michael P Vitek, Christopher B Shields
OBJECTIVE: Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG112 promotes remyelination and improves functional recovery in lysolecithin induced focal demyelination in the white matter of spinal cord in mice...
April 2013: Journal of Neurology & Neurophysiology
Oleg Butovsky, Mark P Jedrychowski, Ron Cialic, Susanne Krasemann, Gopal Murugaiyan, Zain Fanek, David J Greco, Pauline M Wu, Camille E Doykan, Olga Kiner, Robert J Lawson, Matthew P Frosch, Nathalie Pochet, Rachid El Fatimy, Anna M Krichevsky, Steven P Gygi, Hans Lassmann, James Berry, Merit E Cudkowicz, Howard L Weiner
OBJECTIVE: To investigate miR-155 in the SOD1 mouse model and human sporadic and familial amyotrophic lateral sclerosis (ALS). METHODS: NanoString microRNA, microglia and immune gene profiles, protein mass spectrometry, and RNA-seq analyses were measured in spinal cord microglia, splenic monocytes, and spinal cord tissue from SOD1 mice and in spinal cord tissue of familial and sporadic ALS. miR-155 was targeted by genetic ablation or by peripheral or centrally administered anti-miR-155 inhibitor in SOD1 mice...
January 2015: Annals of Neurology
Racine R Emmons, Christopher M Cirnigliaro, Steven C Kirshblum, William A Bauman
OBJECTIVE: To determine the influence of lipid concentration, lipid particle size, and total abdominal fat (TAF) on postprandial lipemic response (PPLr) in persons with spinal cord injury (SCI). METHODS: Thirty-five persons with SCI (17 paraplegia, 18 tetraplegia) and 18 able-bodied (AB) individuals participated. Following a 10-hour fast, blood was drawn for lipids, apolipoprotein (apo) A1 and B concentrations, and low-density (LSP) and high-density (HSP) lipoprotein particle sizes...
November 2014: Journal of Spinal Cord Medicine
Soomin Shin, Katharine A Walz, Angela S Archambault, Julia Sim, Bryan P Bollman, Jessica Koenigsknecht-Talboo, Anne H Cross, David M Holtzman, Gregory F Wu
Apolipoprotein E (ApoE) functions as a ligand in receptor-mediated endocytosis of lipoprotein particles and has been demonstrated to play a role in antigen presentation. To explore the contribution of ApoE during autoimmune central nervous system (CNS) demyelination, we examined the clinical, cellular immune function, and pathologic consequences of experimental autoimmune encephalomyelitis (EAE) induction in ApoE knockout (ApoE(-/-)) mice. We observed reduced clinical severity of EAE in ApoE(-/-) mice in comparison to WT mice that was concomitant with an early reduction of dendritic cells (DCs) followed by a reduction of additional innate cells in the spinal cord at the peak of disease without any differences in axonal damage...
June 15, 2014: Journal of Neuroimmunology
Xin Yan, Fan Yang, Jan Lukas, Martin Witt, Andreas Wree, Arndt Rolfs, Jiankai Luo
Niemann-Pick disease type C1 (NPC1) is a neurodegenerative disease with various progressive pathological features, for example, neuronal loss, dysmyelination, abnormal axon swelling, and gliosis, in the brain. Pathological activation of p38-mitogen-activated protein kinase (MAPK) results in hyperphosphorylation of tau protein, which contributes to the development of neurodegenerative diseases. In this study, axonal varicosities or spheroids and presynaptic aggregates in the spinal cord of the Npc1 mutant mice were found from postnatal day (P) 35 onwards, as indicated by the increased hyperphosphorylated neurofilament and synaptophysin immunoreactivity as well as the findings from electron microscopy...
July 2014: Glia
Ruihua Wang, Jun Hong, Miaomiao Lu, Jessica E Neil, Michael P Vitek, Xiaozhi Liu, David S Warner, Fengqiao Li, Huaxin Sheng
Apolipoprotein E (apoE), a plasma protein responsible for transporting lipid and cholesterol, modulates responses of the central nervous system to injury. Small peptides derived from the receptor-binding region of apoE can simulate some important bioactivities of apoE holoprotein and offer neuroprotection against brain injury. We tested whether COG1410, an apoE-mimetic peptide, provides protection in a rat model of spinal cord injury (SCI). Traumatic injury was created at T8 by a cortical impact device. Injured rats were randomized to four treatment groups: vehicle, 0...
July 2014: Journal of Neuroscience Research
Miki Oono, Ayako Okado-Matsumoto, Akemi Shodai, Akemi Ido, Yasuyuki Ohta, Koji Abe, Takashi Ayaki, Hidefumi Ito, Ryosuke Takahashi, Naoyuki Taniguchi, Makoto Urushitani
Although the aberrant assembly of mutant superoxide dismutase 1 (mSOD1) is implicated in the pathogenesis of familial amyotrophic lateral sclerosis (ALS), the molecular basis of superoxide dismutase 1 (SOD1) oligomerization remains undetermined. We investigated the roles of transglutaminase 2 (TG2), an endogenous cross-linker in mSOD1-linked ALS. TG2 interacted preferentially with mSOD1 and promoted its oligomerization in transfected cells. Purified TG2 directly oligomerized recombinant mutant SOD1 and the apo-form of the wild-type SOD1 proteins in a calcium-dependent manner, indicating that misfolded SOD1 is a substrate of TG2...
February 2014: Journal of Neurochemistry
Mattia Falconi, Federico Iacovelli, Alessandro Desideri
Familial amyotrophic lateral sclerosis caused by mutations in copper-zinc superoxide dismutase (SOD1) is characterized by the presence of SOD1-rich inclusions in spinal cords. It has been shown that a reduced intra-subunit disulfide bridge apo-SOD1 can rapidly initiate fibrillation forming an inter-subunits disulfide under mild, physiologically accessible conditions. Once initiated, elongation can proceed via recruitment of either apo or partially metallated disulfide-intact SOD1 and the presence of copper, but not zinc, ions inhibit fibrillation...
September 2013: Journal of Molecular Modeling
Catherine A Dayger, Jenna S Rosenberg, Clayton Winkler, Scott Foster, Ellen Witkowski, Ted S Benice, Larry S Sherman, Jacob Raber
Multiple sclerosis (MS) is an inflammatory demyelinating disease characterized by sensory, motor, and cognitive impairments. Apolipoprotein E (apoE) plays an important role in cholesterol and lipid metabolism in the brain and in susceptibility to cognitive impairment and pathology following brain injury. Studies in mice with a mild form of experimental autoimmune encephalomyelitis (EAE), an MS animal model, support only protective roles for apoE in MS. We examined behavioral and cognitive changes prior to onset of clinical disease and the onset and progression of a more severe form of EAE in female Apoe(-/-) and C57Bl/6 wild-type mice...
February 2013: Pharmacology, Biochemistry, and Behavior
Per Zetterström, Karin S Graffmo, Peter M Andersen, Thomas Brännström, Stefan L Marklund
Mutant superoxide dismutase-1 (SOD1) has an unidentified toxic property that provokes ALS. Several ALS-linked SOD1 mutations cause long C-terminal truncations, which suggests that common cytotoxic SOD1 conformational species should be misfolded and that the C-terminal end cannot be involved. The cytotoxicity may arise from interaction of cellular proteins with misfolded SOD1 species. Here we specifically immunocaptured misfolded SOD1 by the C-terminal end, from extracts of spinal cords from transgenic ALS model mice...
June 10, 2011: Journal of Biological Chemistry
Timothy W Rhoads, Nathan I Lopez, Daniel R Zollinger, Jeffrey T Morré, Brian L Arbogast, Claudia S Maier, Linda DeNoyer, Joseph S Beckman
Metals are key cofactors for many proteins, yet quantifying the metals bound to specific proteins is a persistent challenge in vivo. We have developed a rapid and sensitive method using electrospray ionization mass spectrometry to measure Cu,Zn superoxide dismutase (SOD1) directly from the spinal cord of SOD1-overexpressing transgenic rats. Metal dyshomeostasis has been implicated in motor neuron death in amyotrophic lateral sclerosis (ALS). Using the assay, SOD1 was directly measured from 100 μg of spinal cord, allowing for anatomical quantitation of apo, metal-deficient, and holo SOD1...
August 1, 2011: Analytical Biochemistry
Chongyi Sun, Guangrong Ji, Qingpeng Liu, Meng Yao
The association between apolipoprotein E (APOE) epsilon 4 (ε4) allele and outcomes of traumatic spinal cord injury (SCI) is still controversial and ambiguous. The objective of this study was to test the hypothesis that APOE polymorphisms are associated with outcomes after SCI in Chinese Han patients. APOE polymorphisms were determined in 100 patients with cervical SCI (C3-C8). The genotype frequency of this polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism assay...
October 2011: Molecular Biology Reports
Shigeko Takeuchi, Noriko Fujiwara, Akemi Ido, Miki Oono, Yuki Takeuchi, Minako Tateno, Keiichiro Suzuki, Ryosuke Takahashi, Ikuo Tooyama, Naoyuki Taniguchi, Jean-Pierre Julien, Makoto Urushitani
Vaccinations targeting extracellular superoxide dismutase 1 (SOD1) mutants are beneficial in mouse models of amyotrophic lateral sclerosis (ALS). Because of its misfolded nature, wild-type nonmetallated SOD1 protein (WT-apo) may have therapeutic application for vaccination of various SOD1 mutants. We compared the effects of WT-apo to those of a G93A SOD1 vaccine in low-copy G93A SOD1 transgenic mice. Both SOD1 vaccines induced antibody against G93A SOD1 and significantly delayed disease onset compared with saline/adjuvant controls...
October 2010: Journal of Neuropathology and Experimental Neurology
Kelly P Arbour-Nicitopoulos, Kathleen A Martin Ginis, A E Latimer
UNLABELLED: Arbour-Nicitopoulos KP, Martin Ginis KA, Latimer AE. Planning, leisure-time physical activity, and coping self-efficacy in persons with spinal cord injury: a randomized controlled trial. OBJECTIVE: To examine the effects of action and coping planning (ACP) on leisure-time physical activity (LTPA) and coping self-efficacy in exercise initiates living with spinal cord injury (SCI). DESIGN: Ten-week, single-blind randomized controlled trial...
December 2009: Archives of Physical Medicine and Rehabilitation
Matthias Setzer, Frank D Vrionis, Elvis J Hermann, Volker Seifert, Gerhard Marquardt
OBJECT: The authors examined a possible association between apolipoprotein E (APOE) gene polymorphism and the outcome after anterior microsurgical decompression in patients with cervical spondylotic myelopathy (CSM). METHODS: The authors conducted a prospective study of 60 consecutive patients (40 men, 20 women) with CSM who underwent anterior microsurgical decompression. The patients ranged in age from 26 to 86 years (mean 61.5 +/- 14.6 years). Neurological deficits were classified according to the modified Japanese Orthopaedic Association Scale...
December 2009: Journal of Neurosurgery. Spine
Madhuri Chattopadhyay, Armando Durazo, Se Hui Sohn, Cynthia D Strong, Edith B Gralla, Julian P Whitelegge, Joan Selverstone Valentine
Familial amyotrophic lateral sclerosis (fALS) caused by mutations in copper-zinc superoxide dismutase (SOD1) is characterized by the presence of SOD1-rich inclusions in spinal cords. Similar inclusions observed in fALS transgenic mice have a fibrillar appearance suggestive of amyloid structure. Metal-free apo-SOD1 is a relatively stable protein and has been shown to form amyloid fibers in vitro only when it has been subjected to severely destabilizing conditions, such as low pH or reduction of its disulfide bonds...
December 2, 2008: Proceedings of the National Academy of Sciences of the United States of America
Venkata Ramesh Dasari, Krishna Kumar Veeravalli, Kay L Saving, Meena Gujrati, Dan Fassett, Jeffrey D Klopfenstein, Dzung H Dinh, Jasti S Rao
The neurotransmitter glutamate mediates excitatory synaptic transmission in the brain and spinal cord. In pathological conditions massive glutamate release reaches near millimolar concentrations in the extracellular space and contributes to neuron degeneration and death. In the present study, we demonstrate a neuroprotective role for human umbilical cord blood stem cells (hUCB) against glutamate-induced apoptosis in cultured rat cortical neurons. Microarray analysis shows the upregulation of stress pathway genes after glutamate toxicity of neurons, while in cocultures with hUCB, survival pathway genes were upregulated...
December 2008: Neurobiology of Disease
Daniel Offen, Yael Barhum, Eldad Melamed, Norbert Embacher, Christoph Schindler, Gerhard Ransmayr
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons in the cerebral cortex, brain stem, and spinal cord. Most cases (90%) are classified as sporadic ALS (sALS). The remainder 10% are inherited and referred to as familial ALS, and 2% of instances are due to mutations in Cu/Zn superoxide dismutase (SOD1). Using cDNA microarray on postmortem spinal cord specimens of four sALS patients compared to four age-matched nonneurological controls, we found major changes in the expression of mRNA in 60 genes including increase of cathepsin B and cathepsin D (by the factors 2 and 2...
June 2009: Journal of Molecular Neuroscience: MN
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