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APP transport

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https://www.readbyqxmd.com/read/28106559/abca1-deficiency-affects-basal-cognitive-deficits-and-dendritic-density-in-mice
#1
Nicholas F Fitz, Alexis Y Carter, Victor Tapias, Emilie L Castranio, Ravindra Kodali, Iliya Lefterov, Radosveta Koldamova
ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoproteins and regulates the generation of high density lipoproteins. Previously, we have shown that lack of Abca1 significantly increases amyloid deposition and cognitive deficits in Alzheimer's disease model mice expressing human amyloid-β protein precursor (APP). The goal of this study was to determine if ABCA1 plays a role in memory deficits caused by amyloid-β (Aβ) oligomers and examine neurite architecture of pyramidal hippocampal neurons...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28053030/tau-isoforms-imbalance-impairs-the-axonal-transport-of-the-amyloid-precursor-protein-in-human-neurons
#2
Valentina Lacovich, Sonia L Espindola, Matías Alloatti, Victorio Pozo Devoto, Lucas E Cromberg, Mária E Čarná, Giancarlo Forte, Jean-Marc Gallo, Luciana Bruno, Gorazd B Stokin, M Elena Avale, Tomás L Falzone
: Tau, as a microtubule (MT)-associated protein, participates in key neuronal functions such as the regulation of MT 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) MT binding repeats. Although tau isoforms are balanced in the normal adult human brain, imbalances in 3R:4R ratio have been tightly associated with the pathogenesis of several neurodegenerative disorders, yet the underlying molecular mechanisms remain elusive...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28028177/autophagy-mediated-regulation-of-bace1-trafficking-and-degradation
#3
Tuancheng Feng, Prasad Tammineni, Chanchal Agrawal, Yu Young Jeong, Qian Cai
Beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the major neuronal beta-secretase for amyloid-beta (Abeta) generation, and is degraded in lysosomes. The autophagy-lysosomal system plays a key role in the maintenance of cellular homeostasis in neurons. Recent studies established that nascent autophagosomes in distal axons move predominantly in the retrograde direction toward the soma, where mature lysosomes are mainly located. However, it remains unknown whether autophagy plays a critical role in regulation of BACE1 trafficking and degradation...
December 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28005987/metabolic-characterization-of-intact-cells-reveals-intracellular-amyloid-beta-but-not-its-precursor-protein-to-reduce-mitochondrial-respiration
#4
Patrick M Schaefer, Bjoern von Einem, Paul Walther, Enrico Calzia, Christine A F von Arnim
One hallmark of Alzheimer´s disease are senile plaques consisting of amyloid beta (Aβ), which derives from the processing of the amyloid precursor protein (APP). Mitochondrial dysfunction has been linked to the pathogenesis of Alzheimer´s disease and both Aβ and APP have been reported to affect mitochondrial function in isolated systems. However, in intact cells, considering a physiological localization of APP and Aβ, it is pending what triggers the mitochondrial defect. Thus, the aim of this study was to dissect the impact of APP versus Aβ in inducing mitochondrial alterations with respect to their subcellular localization...
2016: PloS One
https://www.readbyqxmd.com/read/28000370/amyloid-precursor-protein-traffics-from-the-golgi-directly-to-early-endosomes-in-an-arl5b-and-ap4-dependent-pathway
#5
Wei Hong Toh, Jing Zhi A Tan, Khalisah L Zulkefli, Fiona J Houghton, Paul A Gleeson
The intracellular trafficking and proteolytic processing of the membrane-bound amyloid precursor protein (APP) are co-ordinated events leading to the generation of pathogenic amyloid-beta (Aβ) peptides. The membrane transport of newly synthesised APP from the Golgi to the endolysosomal system is not well defined, yet is likely to be critical for regulating its processing by β-secretase (BACE1) and γ-secretase. Here we show that the majority of newly synthesised APP is transported from the trans-Golgi network (TGN) directly to early endosomes and then subsequently to the late endosomes/lysosomes with very little transported to the cell surface...
December 20, 2016: Traffic
https://www.readbyqxmd.com/read/28000173/in-vitro-evaluation-of-absorption-characteristics-of-peramivir-for-oral-delivery
#6
Ying Li, Zhiyuan Wang, Xin Li, Wei Gong, Xiangyang Xie, Yang Yang, Wu Zhong, Aiping Zheng
BACKGROUND AND OBJECTIVE: Peramivir is a novel antiviral agent approved for the treatment of severe influenza. However, the development of oral formulation of peramivir has been severely hurdled by poor bioavailability (human, ≤3%). The present work aims to evaluate oral permeability characteristics of peramivir. METHODS: In vitro gastrointestinal stability, metabolic stability in human intestinal S9 fraction and Caco-2 permeability were performed. The liquid chromatography with tandem mass spectrometric (LC-MS/MS) was used to quantify peramivir in buffer and biological sample...
December 21, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27993762/smartphone-apps-for-measuring-human-health-and-climate-change-co-benefits-a-comparison-and-quality-rating-of-available-apps
#7
Rachel K Sullivan, Samantha Marsh, Jakob Halvarsson, Michelle Holdsworth, Wilma Waterlander, Maartje P Poelman, Jennifer Ann Salmond, Hayley Christian, Lenny Sc Koh, Janet E Cade, John C Spence, Alistair Woodward, Ralph Maddison
BACKGROUND: Climate change and the burden of noncommunicable diseases are major global challenges. Opportunities exist to investigate health and climate change co-benefits through a shift from motorized to active transport (walking and cycling) and a shift in dietary patterns away from a globalized diet to reduced consumption of meat and energy dense foods. Given the ubiquitous use and proliferation of smartphone apps, an opportunity exists to use this technology to capture individual travel and dietary behavior and the associated impact on the environment and health...
December 19, 2016: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/27932950/amyloid-precursor-proteins-are-dynamically-trafficked-and-processed-during-neuronal-development
#8
Jenna M Ramaker, Robert S Cargill, Tracy L Swanson, Hanil Quirindongo, Marlène Cassar, Doris Kretzschmar, Philip F Copenhaver
Proteolytic processing of the Amyloid Precursor Protein (APP) produces beta-amyloid (Aβ) peptide fragments that accumulate in Alzheimer's Disease (AD), but APP may also regulate multiple aspects of neuronal development, albeit via mechanisms that are not well understood. APP is a member of a family of transmembrane glycoproteins expressed by all higher organisms, including two mammalian orthologs (APLP1 and APLP2) that have complicated investigations into the specific activities of APP. By comparison, insects express only a single APP-related protein (APP-Like, or APPL) that contains the same protein interaction domains identified in APP...
2016: Frontiers in Molecular Neuroscience
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
#9
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
#10
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...
2017: 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
#11
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
#12
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
#13
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
#14
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
#15
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/wzb117-2-fluoro-6-m-hydroxybenzoyloxy-phenyl-m-hydroxybenzoate-inhibits-glut1-mediated-sugar-transport-by-binding-reversibly-at-the-exofacial-sugar-binding-site
#16
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 glucose transport protein 1 (GLUT1) and examines the transporter isoform specificity of inhibition. WZB117 reversibly and competitively inhibits erythrocyte 3-O-methylglucose (3MG) uptake with Ki(app) = 6 μm but is a noncompetitive inhibitor of sugar exit...
December 23, 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
#17
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
#18
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
#19
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
#20
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...
January 2017: Biochimica et Biophysica Acta
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