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APP transport

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https://www.readbyqxmd.com/read/27915995/lack-of-p-glycoprotein-results-in-impairment-of-removal-of-beta-amyloid-and-increased-intraparenchymal-cerebral-amyloid-angiopathy-after-active-immunization-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#1
Sascha Brückmann, Anja Brenn, Markus Grube, Katharina Niedrig, Silva Holtfreter, Oliver von Bohlen Und Halbach, Martin Groschup, Markus Keller, Silke Vogelgesang
Immunization against beta-amyloid (Aβ) reduces cerebral Aβ deposits and improves cognitive capacities in transgenic mouse models, and thus has been considered a promising disease-modifying therapeutic approach for Alzheimer's disease (AD). Although clinical trials in AD patients have yielded evidence for clearance of parenchymal Aβ plaques, Aβ increases in blood vessels of treated patients. We hypothesize that an age-related decline in the mechanisms that clear Aβ from the brain might be at least in part responsible for the failure to purge and re-distribute Aβ...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27911305/nitrosylation-of-vesicular-transporters-in-brain-of-amyloid-precursor-protein-presenilin-1-double-transgenic-mice
#2
Ying Wang, Zhu Zhou, Hua Tan, Shenghua Zhu, Yiran Wang, Yingxia Sun, Xin-Min Li, Jun-Feng Wang
Nitric oxide can attack thiol groups of cysteine residues in proteins and induce protein cysteine S-nitrosylation. Cholinergic and glutamatergic systems are dysregulated in Alzheimer's disease. Vesicular acetylcholine transporter (VAChT) and vesicular glutamate transporter 1 (VGLUT1) are important in packaging acetylcholine and glutamate into vesicles, which is an important step for neurotransmission. Previously we found that VAChT and VGLUT1 can be nitrosylated and that S-nitrosylation of these transporters inhibits vesicular uptake of acetylcholine and glutamate...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911303/amylin-treatment-reduces-neuroinflammation-and-ameliorates-abnormal-patterns-of-gene-expression-in%C3%A2-the-cerebral-cortex-of-an-alzheimer-s-disease-mouse-model
#3
Erming Wang, Haihao Zhu, Xiaofan Wang, Adam Gower, Max Wallack, Jan Krzysztof Blusztajn, Neil Kowall, Wei Qiao Qiu
Our recent study has demonstrated that peripheral amylin treatment reduces the amyloid pathology in the brain of Alzheimer's disease (AD) mouse models, and improves their learning and memory. We hypothesized that the beneficial effects of amylin for AD was beyond reducing the amyloids in the brain, and have now directly tested the actions of amylin on other aspects of AD pathogenesis, especially neuroinflammation. A 10-week course of peripheral amylin treatment significantly reduced levels of cerebral inflammation markers, Cd68 and Iba1, in amyloid precursor protein (APP) transgenic mice...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27904476/impairment-of-the-nerve-growth-factor-pathway-driving-amyloid-accumulation-in-cholinergic-neurons-the-incipit-of-the-alzheimer-s-disease-story
#4
REVIEW
Viviana Triaca, Pietro Calissano
The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor (NGF) alterations in sporadic Alzheimer's disease (AD), an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons (BFCN), is one of the first homeostatic systems affected in prodromal AD...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27891669/a-molecular-dynamics-study-of-the-binary-complexes-of-app-jip1-and-the-cargo-binding-domain-of-klc
#5
Cooper A Taylor, Bill R Miller, Soleil S Shah, Carol A Parish
Mutations in the amyloid precursor protein (APP) are responsible for the formation of amyloid-β peptides. These peptides play a role in Alzheimer's and other dementia-related diseases. The cargo binding domain of the kinesin-1 light chain motor protein (KLC1) may be responsible for transporting APP either directly or via interaction with C-jun N-terminal kinase-interacting protein 1 (JIP1). However, to date there has been no direct experimental or computational assessment of such binding at the atomistic level...
November 7, 2016: Proteins
https://www.readbyqxmd.com/read/27852778/the-effects-of-peripheral-and-central-high-insulin-on-brain-insulin-signaling-and-amyloid-%C3%AE-in-young-and-old-app-ps1-mice
#6
Molly Stanley, Shannon L Macauley, Emily E Caesar, Lauren J Koscal, Will Moritz, Grace O Robinson, Joseph Roh, Jennifer Keyser, Hong Jiang, David M Holtzman
: Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APPswe/PS1dE9 transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls...
November 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27837099/tau-isoforms-imbalance-impairs-the-axonal-transport-of-the-amyloid-precursor-protein-in-human-neurons
#7
Valentina Lacovich, Sonia L Espindola, Matías Alloatti, Victorio Pozo Devoto, Lucas Cromberg, Mária Čarná, Giancarlo Forte, Jean-Marc Gallo, Luciana Bruno, Gorazd B Stokin, M Elena Avale, Tomás L Falzone
: Tau, as a microtubule-associated protein, participates in key neuronal functions such as the regulation of microtubule dynamics, axonal transport and neurite outgrowth. Alternative splicing of exon 10 in the tau primary transcript gives rise to protein isoforms with three (3R) or four (4R) microtubule binding repeats. While tau isoforms are balanced in the normal adult human brain, imbalances in 3R:4R ratio have been tightly associated to the pathogenesis of several neurodegenerative disorders, yet the underlying molecular mechanisms remain elusive...
November 11, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27836974/wzb117-inhibits-glut1-mediated-sugar-transport-by-binding-reversibly-at-the-exofacial-sugar-binding-site
#8
Ogooluwa A Ojelabi, Kenneth P Lloyd, Andrew H Simon, Julie K De Zutter, Anthony Carruthers
WZB117 (2-fluoro-6-(m-hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits passive sugar transport in human erythrocytes and cancer cell lines and, by limiting glycolysis, inhibits tumor growth in mice. This study explores how WZB117 inhibits the erythrocyte sugar transporter GLUT1 and examines the transporter isoform-specificity of inhibition. WZB117 reversibly and competitively inhibits erythrocyte 3-O-methylglucose (3MG) uptake with Ki(app) = 6 microM but is a noncompetitive inhibitor of sugar exit. Cytochalasin B (CB) is a reversible, noncompetitive inhibitor of 3MG uptake with Ki(app) = 0...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27834125/role-of-ageing-and-oxidative-stress-in-regulation-of-amyloid-degrading-enzymes-and-development-of-neurodegeneration
#9
Natalia N Nalivaeva, Anthony J Turner
The accumulation of cerebral amyloid β-peptide (Aβ) is a key precipitating factor for neuronal cell death in Alzheimer's disease (AD). However, brain Aβ levels are modifiable since there is a balance between its formation from the amyloid precursor protein (APP) and its removal by clearance mechanisms, which can be either through proteolysis or by protein binding and subsequent transport). Among the major enzymes degrading brain Aβ are several zinc-proteases: neprilysin (NEP), its homologues NEP2 and the endothelin converting enzymes (ECE-1 and -2) and also the insulin-degrading enzyme (IDE)...
November 10, 2016: Current Aging Science
https://www.readbyqxmd.com/read/27829865/improvement-of-electroacupuncture-on-app-ps1-transgenic-mice-in-spatial-learning-and-memory-probably-due-to-expression-of-a%C3%AE-and-lrp1-in-hippocampus
#10
Xin Wang, Yanhuan Miao, Jiawula Abulizi, Fu Li, Yuping Mo, Weiguo Xue, Zhigang Li
Objectives. To explore the alterations of β-amyloid (Aβ) and low density lipoprotein receptor-related protein-1 (LRP1) in APP/PS1 mice after electroacupuncture (EA) treatment and further to explore the mechanism. Methods. Forty 6-month-old APP/PS1 mice were randomly divided into a model group and an EA group, with twenty wild-type mice used as a normal control group. Mice in the EA group were treated with EA at GV 20 (băi huì) and bilateral KI 1 (yŏng quán) acupoints for 6 weeks. The Morris water maze was applied to assess the spatial memory in behavior...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27829662/high-glucose-upregulates-bace1-mediated-a%C3%AE-production-through-ros-dependent-hif-1%C3%AE-and-lxr%C3%AE-abca1-regulated-lipid-raft-reorganization-in-sk-n-mc-cells
#11
Hyun Jik Lee, Jung Min Ryu, Young Hyun Jung, Sei-Jung Lee, Jeong Yeon Kim, Sang Hun Lee, In Koo Hwang, Je Kyung Seong, Ho Jae Han
There is an accumulation of evidence indicating that the risk of Alzheimer's disease is associated with diabetes mellitus, an indicator of high glucose concentrations in blood plasma. This study investigated the effect of high glucose on BACE1 expression and amyloidogenesis in vivo, and we present details of the mechanism associated with those effects. Our results, using ZLC and ZDF rat models, showed that ZDF rats have high levels of amyloid-beta (Aβ), phosphorylated tau, BACE1, and APP-C99. In vitro result with mouse hippocampal neuron and SK-N-MC, high glucose stimulated Aβ secretion and apoptosis in a dose-dependent manner...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27818272/tetraspanin-3-a-central-endocytic-membrane-component-regulating-the-expression-of-adam10-presenilin-and-the-amyloid-precursor-protein
#12
Lisa Seipold, Markus Damme, Johannes Prox, Björn Rabe, Petr Kasparek, Radislav Sedlacek, Hermann Altmeppen, Michael Willem, Barry Boland, Markus Glatzel, Paul Saftig
Despite existing knowledge about the role of the A Disintegrin and Metalloproteinase 10 (ADAM10) as the α-secretase involved in the non-amyloidogenic processing of the amyloid precursor protein (APP) and Notch signalling we have only limited information about its regulation. In this study, we have identified ADAM10 interactors using a split ubiquitin yeast two hybrid approach. Tetraspanin 3 (Tspan3), which is highly expressed in the murine brain and elevated in brains of Alzheimer´s disease (AD) patients, was identified and confirmed to bind ADAM10 by co-immunoprecipitation experiments in mammalian cells in complex with APP and the γ-secretase protease presenilin...
November 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27775390/using-drinking-data-and-pharmacokinetic-modeling-to-calibrate-transport-model-and-blind-deconvolution-based-data-analysis-software-for-transdermal-alcohol-biosensors
#13
Zheng Dai, I G Rosen, Chuming Wang, Nancy Barnett, Susan E Luczak
Alcohol researchers/clinicians have two ways to collect subject /patient field data, standard-drink self-report and the breath analyzer, neither of which is passive or accurate because active subject participation is required. Transdermal alcohol sensors have been developed to measure transdermal alcohol concentration (TAC), but they are used primarily as abstinence monitors because converting TAC into more meaningful blood/breath alcohol concentration (BAC/BrAC) is difficult. In this paper, BAC/BrAC is estimated from TAC by first calibrating forward distributed parameter-based convolution models for ethanol transport from the blood through the skin using patient-collected drinking data for a single drinking episode and a nonlinear pharmacokinetic metabolic absorption/elimination model to estimate BAC...
October 1, 2016: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/27771897/profiling-of-signaling-proteins-in-penumbra-after-focal-photothrombotic-infarct-in-the-rat-brain-cortex
#14
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27662313/neuroprotective-effect-of-trem-2-in-aging-and-alzheimer-s-disease-model
#15
Animesh Alexander Raha, James W Henderson, Simon R W Stott, Romina Vuono, Simona Foscarin, Robert P Friedland, Shahid H Zaman, Ruma Raha-Chowdhury
Neuroinflammation and activation of innate immunity are early events in neurodegenerative diseases including Alzheimer's disease (AD). Recently, a rare mutation in the gene Triggering receptor expressed on myeloid cells 2 (TREM2) has been associated with a substantial increase in the risk of developing late onset AD. To uncover the molecular mechanisms underlying this association, we investigated the RNA and protein expression of TREM2 in APP/PS1 transgenic mice. Our findings suggest that TREM2 not only plays a critical role in inflammation, but is also involved in neuronal cell survival and in neurogenesis...
September 20, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27639976/implications-of-the-change-in-confinement-status-of-a-heterogeneous-aquifer-for-scale-dependent-dispersion-and-mass-transfer-processes
#16
D Pedretti, A Molinari, C Fallico, S Guzzi
A series of experimental tracer tests were performed to explore the implications of the change in the pressure status of a heterogeneous bimodal aquifer for scale-dependent dispersion and mass-transfer processes. The sandbox was filled with sands and gravel channels and patches to form an alluvial-like bimodal aquifer. We performed multiple injections of a conservative tracer from 26 different locations of the sandbox and interpreted the resulting depth-integrated breakthrough curves (BTCs) at the central pumping well to obtain a scale-dependent distribution of local and field-integrated apparent longitudinal dispersivity (respectively, αL(loc) and αL(app))...
September 9, 2016: Journal of Contaminant Hydrology
https://www.readbyqxmd.com/read/27629715/soluble-conformers-of-a%C3%AE-and-tau-alter-selective-proteins-governing-axonal-transport
#17
Mathew A Sherman, Michael LaCroix, Fatou Amar, Megan E Larson, Colleen Forster, Adriano Aguzzi, David A Bennett, Martin Ramsden, Sylvain E Lesné
UNLABELLED: Despite the demonstration that amyloid-β (Aβ) can trigger increased tau phosphorylation and neurofibrillary tangle (NFT) formation in vivo, the molecular link associating Aβ and tau pathologies remains ill defined. Here, we observed that exposure of cultured primary neurons to Aβ trimers isolated from brain tissue of subjects with Alzheimer's disease led to a specific conformational change of tau detected by the antibody Alz50. A similar association was supported by postmortem human brain analyses...
September 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27616657/signal-attenuation-of-pfg-restricted-anomalous-diffusions-in-plate-sphere-and-cylinder
#18
Guoxing Lin, Shaokuan Zheng, Xinli Liao
Pulsed field gradient (PFG) NMR is a noninvasive tool to study anomalous diffusion, which exists widely in many systems such as in polymer or biological systems, in porous material, in single file structures and in fractal geometries. In a real system, the diffusion could be a restricted or a tortuous anomalous diffusion, rather than a free diffusion as the domains for fast and slow transport could coexist. Though there are signal attenuation expressions for free anomalous diffusion in literature, the signal attenuation formalisms for restricted anomalous diffusion is very limited, except for a restricted time-fractional diffusion within a plate reported recently...
August 31, 2016: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/27592741/acute-axonal-damage-in-three-different-murine-models-of-multiple-sclerosis-a-comparative-approach
#19
Katharina Marie Höflich, Cordian Beyer, Tim Clarner, Christoph Schmitz, Stella Nyamoya, Markus Kipp, Tanja Hochstrasser
Axonal damage has been identified as a significant contributor to permanent clinical disability in multiple sclerosis. In the context of demyelinating disorders, this destructive event can be the result of inflammation, demyelination and/or the activation of innate defense cells such as microglia or monocytes. The relative contribution of each of these variables to acute axonal injury is, however, unknown. In the present study, we compared the extent of acute axonal damage in three different murine demyelination models using anti-amyloid precursor protein (APP) immunohistochemistry...
November 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27585269/performance-of-electroremediation-in-real-contaminated-sediments-using-a-big-cell-periodic-voltage-and-innovative-surfactants
#20
John N Hahladakis, Antonis Latsos, Evangelos Gidarakos
The present work focused on evaluating the electrokinetic (EK) treatment of real contaminated sediments with toxic metals and polycyclic aromatic hydrocarbons (PAHs), using a big laboratory EK cell, periodic voltage and recently tested non-ionic surfactants. The results indicated that the "day on-night off" application mode of voltage, in conjunction with the selected solubilising agents, favoured the overall EK process. Arsenic, nickel and chromium exhibited the highest removal percentages, obtaining 83%, 67% and 63%, respectively, while zinc and lead attained 54% and 41% at the maximum...
December 15, 2016: Journal of Hazardous Materials
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