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https://www.readbyqxmd.com/read/28059785/amylin-enhances-amyloid-%C3%AE-peptide-brain-to-blood-efflux-across-the-blood-brain-barrier
#1
Loqman A Mohamed, Haihao Zhu, Youssef M Mousa, Erming Wang, Wei Qiao Qiu, Amal Kaddoumi
Findings from Alzheimer's disease (AD) mouse models showed that amylin treatment improved AD pathology and enhanced amyloid-β (Aβ) brain to blood clearance; however, the mechanism was not investigated. Using the Tg2576 AD mouse model, a single intraperitoneal injection of amylin significantly increased Aβ serum levels, and the effect was abolished by AC253, an amylin receptor antagonist, suggesting that amylin effect could be mediated by its receptor. Subsequent mechanistic studies showed amylin enhanced Aβ transport across a cell-based model of the blood-brain barrier (BBB), an effect that was abolished when the amylin receptor was inhibited by two amylin antagonists and by siRNA knockdown of amylin receptor Ramp3...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28012205/activated-%C3%AE-2-macroglobulin-induces-mesenchymal-cellular-migration-of-raw264-7-cells-through-low-density-lipoprotein-receptor-related-protein-1
#2
Darío G Ferrer, Virginia Actis Dato, Javier R Jaldín Fincati, Valeria E Lorenc, María C Sánchez, Gustavo A Chiabrando
Distinct modes of cell migration contribute to diverse types of cell movements. The mesenchymal mode is characterized by a multistep cycle of membrane protrusion, the formation of focal adhesion, and the stabilization at the leading edge associated with the degradation of extracellular matrix (ECM) components and with regulated extracellular proteolysis. Both α2 -Macroglobulin (α2 M) and its receptor, low density lipoprotein receptor-related protein 1 (LRP1), play important roles in inflammatory processes, by controlling the extracellular activity of several proteases...
December 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27986809/urokinase-type-plasminogen-activator-upa-binding-to-the-upa-receptor-upar-promotes-axonal-regeneration-in-the-central-nervous-system
#3
Paola Merino, Ariel Diaz, Valerie Jeanneret, Fang Wu, Enrique Torre, Lihong Cheng, Manuel Yepes
Axonal injury is a common cause of neurological dysfunction. Unfortunately, in contrast to axons from the peripheral nervous system, the limited capacity of regeneration of central nervous system (CNS) axons is a major obstacle for functional recovery in patients suffering neurological diseases that involve the subcortical white matter. Urokinase-type plasminogen activator (uPA) is a serine proteinase that upon binding to the urokinase-type plasminogen activator receptor (uPAR) catalyzes the conversion of plasminogen into plasmin on the cell surface...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27979811/high-glucose-facilitated-endothelial-heparanase-transfer-to-the-cardiomyocyte-modifies-its-cell-death-signature
#4
Fulong Wang, Jocelyn Jia, Nathaniel Lal, Dahai Zhang, Amy Pei-Ling Chiu, Andrea Wan, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
AIMS: The secretion of enzymatically active heparanase (Hep(A)) has been implicated as an essential metabolic adaptation in the heart following diabetes. However, the regulation and function of the enzymatically inactive heparanase (Hep(L)) remain poorly understood. We hypothesized that in response to high glucose (HG) and secretion of Hep(L) from the endothelial cell (EC), Hep(L) uptake and function can protect the cardiomyocyte by modifying its cell death signature. METHODS AND RESULTS: HG promoted both Hep(L) and Hep(A) secretion from microvascular (rat heart micro vessel endothelial cells, RHMEC) and macrovascular (rat aortic endothelial cells, RAOEC) EC...
December 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27959956/mesenchymal-stromal-cells-promote-axonal-outgrowth-alone-and-synergistically-with-astrocytes-via-tpa
#5
Jian-Yong Qian, Michael Chopp, Zhongwu Liu
We reported that mesenchymal stromal cells (MSCs) enhance neurological recovery from experimental stroke and increase tissue plasminogen activator (tPA) expression in astrocytes. Here, we investigate mechanisms by which tPA mediates MSC enhanced axonal outgrowth. Primary murine neurons and astrocytes were isolated from wild-type (WT) and tPA-knockout (KO) cortices of embryos. Mouse MSCs (WT) were purchased from Cognate Inc. Neurons (WT or KO) were seeded in soma side of Xona microfluidic chambers, and astrocytes (WT or KO) and/or MSCs in axon side...
2016: PloS One
https://www.readbyqxmd.com/read/27956551/recombinant-expression-of-the-full-length-ectodomain-of-ldl-receptor-related-protein-1-lrp1-unravels-ph-dependent-conformational-changes-and-the-stoichiometry-of-binding-with-receptor-associated-protein-rap
#6
Camilla De Nardis, Philip Lössl, Maartje van den Biggelaar, Pramod K Madoori, Nadia Leloup, Koen Mertens, Albert J R Heck, Piet Gros
LDL receptor-related protein 1 (LRP1) is a highly modular protein and the largest known mammalian endocytic receptor. LRP1 binds and internalizes many plasma components, playing multiple crucial roles as a scavenger and signaling molecule. One major challenge to studying LRP1 has been that it is difficult to express such a large, highly glycosylated, and cysteine-rich protein, limiting structural studies to LRP1 fragments. Here, we report the first recombinant expression of the complete 61 domains of the LRP1 full-length ectodomain...
December 12, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27933291/endocytosis-and-physiology-insights-from-disabled-2-deficient-mice
#7
REVIEW
Wensi Tao, Robert Moore, Elizabeth R Smith, Xiang-Xi Xu
Disabled-2 (Dab2) is a clathrin and cargo binding endocytic adaptor protein, and cell biology studies revealed that Dab2 plays a role in cellular trafficking of a number of transmembrane receptors and signaling proteins. A PTB/PID domain located in the N-terminus of Dab2 binds the NPXY motif(s) present at the cytoplasmic tails of certain transmembrane proteins/receptors. The membrane receptors reported to bind directly to Dab2 include LDL receptor and its family members LRP1 and LRP2 (megalin), growth factor receptors EGFR and FGFR, and the cell adhesion receptor beta1 integrin...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27931217/lrp1-modulates-the-microglial-immune-response-via-regulation-of-jnk-and-nf-%C3%AE%C2%BAb-signaling-pathways
#8
Longyu Yang, Chia-Chen Liu, Honghua Zheng, Takahisa Kanekiyo, Yuka Atagi, Lin Jia, Daxin Wang, Aurelie N'songo, Dan Can, Huaxi Xu, Xiao-Fen Chen, Guojun Bu
BACKGROUND: Neuroinflammation is characterized by microglial activation and the increased levels of cytokines and chemokines in the central nervous system (CNS). Recent evidence has implicated both beneficial and toxic roles of microglia when over-activated upon nerve injury or in neurodegenerative diseases, including Alzheimer's disease (AD). The low-density lipoprotein receptor-related protein 1 (LRP1) is a major receptor for apolipoprotein E (apoE) and amyloid-β (Aβ), which play critical roles in AD pathogenesis...
December 8, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27924190/network-analysis-of-human-post-mortem-microarrays-reveals-novel-genes-micrornas-and-mechanistic-scenarios-of-potential-importance-in-fighting-huntington-s-disease
#9
Sreedevi Chandrasekaran, Danail Bonchev
Huntington's disease is a progressive neurodegenerative disorder characterized by motor disturbances, cognitive decline, and neuropsychiatric symptoms. In this study, we utilized network-based analysis in an attempt to explore and understand the underlying molecular mechanism and to identify critical molecular players of this disease condition. Using human post-mortem microarrays from three brain regions (cerebellum, frontal cortex and caudate nucleus) we selected in a four-step procedure a seed set of highly modulated genes...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27849881/239-lrp1-an-endocytic-vesicle-trafficking-protein-associated-with-chd-an-unexplored-pathway
#10
Jiuann-Huey Lin, Anupma Jha, Jacob McClreary, Cecilia Lo
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27833152/selenium-binding-lactoferrin-is-taken-into-corneal-epithelial-cells-by-a-receptor-and-prevents-corneal-damage-in-dry-eye-model-animals
#11
Akihiro Higuchi, Hiroyoshi Inoue, Yoshio Kaneko, Erina Oonishi, Kazuo Tsubota
The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases including dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy of Se-lactoferrin eye drops in the tobacco smoke exposure rat dry eye model and short-term rabbit dry eye model, although Diquas eye drops were only effective in the short-term rabbit dry eye model...
November 11, 2016: Scientific Reports
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
#12
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/27824728/evidence-that-ldl-receptor-related-protein-1-acts-as-an-early-injury-detection-receptor-and-activates-c-jun-in-schwann-cells
#13
Andreas Flütsch, Kenneth Henry, Elisabetta Mantuano, Michael S Lam, Masataka Shibayama, Kazuhisa Takahashi, Steven L Gonias, Wendy M Campana
Schwann cells (SCs) detect injury to peripheral nerves and transform phenotypically to respond to injury and facilitate repair. Cell-signaling pathways and changes in gene expression that drive SC phenotypic transformation in injury have been described; however, the SC receptors that detect peripheral nervous system (PNS) injury have not been identified. LDL receptor-related protein 1 (LRP1) is a receptor for numerous ligands, including intracellular proteins released by injured cells and protein components of degenerated myelin...
December 14, 2016: Neuroreport
https://www.readbyqxmd.com/read/27794518/evidence-that-factor-viii-forms-a-bivalent-complex-with-the-low-density-lipoprotein-ldl-receptor-related-protein-1-lrp1-identification-of-cluster-iv-on-lrp1-as-the-major-binding-site
#14
Patricia A Young, Mary Migliorini, Dudley K Strickland
Hemophilia A is a bleeding disorder caused by a deficiency in coagulation factor VIII (fVIII) that affects 1 in 5,000 males. Current prophylactic replacement therapy, although effective, is difficult to maintain due to the cost and frequency of injections. Hepatic clearance of fVIII is mediated by the LDL receptor-related protein 1 (LRP1), a member of the LDL receptor family. Although it is well established that fVIII binds LRP1, the molecular details of this interaction are unclear as most of the studies have been performed using fragments of fVIII and LRP1...
December 9, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27732771/n-linked-glycan-truncation-causes-enhanced-clearance-of-plasma-derived-von-willebrand-factor
#15
J M O'Sullivan, S Aguila, E McRae, S E Ward, O Rawley, P G Fallon, T M Brophy, R J S Preston, L Brady, O Sheils, A Chion, J S O'Donnell
Essentials von Willebrands factor (VWF) glycosylation plays a key role in modulating in vivo clearance. VWF glycoforms were used to examine the role of specific glycan moieties in regulating clearance. Reduction in sialylation resulted in enhanced VWF clearance through asialoglycoprotein receptor. Progressive VWF N-linked glycan trimming resulted in increased macrophage-mediated clearance. Click to hear Dr Denis discuss clearance of von Willebrand factor in a free presentation from the ISTH Academy SUMMARY: Background Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD)...
December 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27701147/cancer-associated-fibroblast-derived-annexin-a6-extracellular-vesicles-support-pancreatic-cancer-aggressiveness
#16
Julie Leca, Sébastien Martinez, Sophie Lac, Jérémy Nigri, Véronique Secq, Marion Rubis, Christian Bressy, Arnauld Sergé, Marie-Noelle Lavaut, Nelson Dusetti, Céline Loncle, Julie Roques, Daniel Pietrasz, Corinne Bousquet, Stéphane Garcia, Samuel Granjeaud, Mehdi Ouaissi, Jean Baptiste Bachet, Christine Brun, Juan L Iovanna, Pascale Zimmermann, Sophie Vasseur, Richard Tomasini
The intratumoral microenvironment, or stroma, is of major importance in the pathobiology of pancreatic ductal adenocarcinoma (PDA), and specific conditions in the stroma may promote increased cancer aggressiveness. We hypothesized that this heterogeneous and evolving compartment drastically influences tumor cell abilities, which in turn influences PDA aggressiveness through crosstalk that is mediated by extracellular vesicles (EVs). Here, we have analyzed the PDA proteomic stromal signature and identified a contribution of the annexin A6/LDL receptor-related protein 1/thrombospondin 1 (ANXA6/LRP1/TSP1) complex in tumor cell crosstalk...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27698954/korean-pine-nut-oil-replacement-decreases-intestinal-lipid-uptake-while-improves-hepatic-lipid-metabolism-in-mice
#17
Shuang Zhu, Soyoung Park, Yeseo Lim, Sunhye Shin, Sung Nim Han
BACKGROUND/OBJECTIVES: Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS: Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks...
October 2016: Nutrition Research and Practice
https://www.readbyqxmd.com/read/27682851/presumed-lrp1-targeting-transport-peptide-delivers-%C3%AE-secretase-inhibitor-to-neurons-in-vitro-with-limited-efficiency
#18
Jong Ah Kim, Tommaso Casalini, Davide Brambilla, Jean-Christophe Leroux
Interfering with the activity of β-secretase to reduce the production of Aβ peptides is a conceivable therapeutic strategy for Alzheimer's disease. However, the development of efficient yet safe inhibitors is hampered by secondary effects, usually linked to the indiscriminate inhibition of other substrates' processing by the targeted enzyme. Based on the spatial compartmentalization of the cleavage of the amyloid precursor protein by β-secretase, we hypothesized that by exploiting the endocytosis receptor low-density lipoprotein receptor-related protein it would be possible to direct an otherwise cell-impermeable inhibitor to the endosomes of neurons, boosting the drug's efficacy and importantly, sparing the off-target effects...
September 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27680891/macrophages-of-genetically-characterized-familial-hypercholesterolaemia-patients-show-up-regulation-of-ldl-receptor-related-proteins
#19
Rafael Escate, Teresa Padro, Maria Borrell-Pages, Rosa Suades, Rosa Aledo, Pedro Mata, Lina Badimon
Familial hypercholesterolaemia (FH) is a major risk for premature coronary heart disease due to severe long-life exposure to high LDL levels. Accumulation of LDL in the vascular wall triggers atherosclerosis with activation of the innate immunity system. Here, we have investigated (i) gene expression of LDLR and LRPs in peripheral blood cells (PBLs) and in differentiated macrophages of young FH-patients; and (ii) whether macrophage from FH patients have a differential response when exposed to high levels of atherogenic LDL...
September 29, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27644406/rapid-hepatic-clearance-of-full-length-ccn-2-ctgf-a-putative-role-for-lrp1-mediated-endocytosis
#20
K G F Gerritsen, N Bovenschen, T Q Nguyen, D Sprengers, M P Koeners, A N van Koppen, J A Joles, R Goldschmeding, R J Kok
CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min)...
December 2016: Journal of Cell Communication and Signaling
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