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https://www.readbyqxmd.com/read/28814781/association-between-lrp1-c766t-polymorphism-and-alzheimer-s-disease-susceptibility-a-meta-analysis
#1
Yun Wang, Shengyuan Liu, Jingjing Wang, Jie Zhang, Yaqiong Hua, Hua Li, Huibiao Tan, Bin Kuai, Biao Wang, Sitong Sheng
Low density lipoprotein receptor-related protein 1 (LRP1) C766T polymorphism (rs1799986) has been extensively investigated for Alzheimer's disease (AD) susceptibility. However, results in different studies have been contradictory. Therefore, we conducted a meta-analysis containing 6455 AD cases and 6304 controls from 26 independent case-control studies to determine whether there was an association between the LRP1 C766T polymorphism and AD susceptibility. The combined analysis showed that there was no significant association between LRP1 C766T polymorphism and AD susceptibility (TT + CT versus CC: OR = 0...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28804736/urokinase-type-plasminogen-activator-upa-and-its-receptor-upar-promote-neurorepair-in-the-ischemic-brain
#2
Paola Merino, Ariel Diaz, Manuel Yepes
Despite the fact that ischemic stroke has been considered a leading cause of mortality in the world, recent advances in our understanding of the pathophysiological mechanisms underlying the ischemic injury and the treatment of acute ischemic stroke patients have led to a sharp decrease in the number of stroke deaths. However, this decrease in stroke mortality has also led to an increase in the number of patients that survive the acute ischemic injury with different degrees of disability. Unfortunately, to this date we do not have an effective therapeutic strategy to promote neurological recovery in these growing population of stroke survivors...
2017: Receptors & Clinical Investigation
https://www.readbyqxmd.com/read/28799085/dimerization-leads-to-changes-in-app-amyloid-precursor-protein-trafficking-mediated-by-lrp1-and-sorla
#3
Simone Eggert, A C Gonzalez, C Thomas, S Schilling, S M Schwarz, C Tischer, V Adam, P Strecker, V Schmidt, T E Willnow, G Hermey, C U Pietrzik, E H Koo, Stefan Kins
Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer's disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization...
August 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28798097/suramin-inhibits-osteoarthritic-cartilage-degradation-by-increasing-extracellular-levels-of-chondroprotective-tissue-inhibitor-of-metalloproteinases-3-timp-3
#4
Anastasios Chanalaris, Christine Doherty, Brian D Marsden, Gabriel Bambridge, Stephen P Wren, Hideaki Nagase, Linda Troeberg
Osteoarthritis is a common degenerative joint disease for which no disease-modifying drugs are currently available. Attempts to treat the disease with small molecule inhibitors of the metalloproteinases that degrade the cartilage matrix have been hampered by a lack of specificity. We aimed to inhibit cartilage degradation by augmenting levels of the endogenous metalloproteinase inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP-3), through blocking its interaction with the endocytic scavenger receptor, low-density lipoprotein receptor-related protein 1 (LRP1)...
August 10, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28783583/influence-of-quercetin-naringenin-and-berberine-on-glucose-transporters-and-insulin-signalling-molecules-in-brain-of-streptozotocin-induced-diabetic-rats
#5
Sandeep M S, Nandini C D
Quercetin, naringenin, and berberine are plant bioactives that can cross the blood-brain barrier and offer neuroprotection. In the present study, we looked into the effect of them on expression of various glucose transporters and key components of brain insulin signalling, namely, insulin receptor substrate 1 (IRS 1), phosphatidyl inositol 3 kinase (PI3K), Akt 1 and low-density lipoprotein receptor-related protein 1 (LRP1) in brain of control, diabetic and bioactive-treated rats by Western blot. Amongst the bioactives tested, quercetin was more potent and restored LRP1 and brain insulin signalling components as well as glucose transporters such as GLUTs 1, 2, 3 and 4 in diabetic animals...
August 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28762182/diet-induced-hypercholesterolemia-alters-liver-glycosaminoglycans-and-associated-lipoprotein-receptors-in-rats
#6
Gangappa Kiran, Ummiti J S Prasada Rao, Paramahans V Salimath, Nandini D Chilkunda
Glycosaminoglycans (GAGs) play an important role in lipoprotein metabolism. In liver, it facilitates the uptake of remnants through receptor-independent endocytosis. However, changes in liver GAGs during diet-induced hypercholesterolemia with normal levels of fat feeding are unknown. Present paper highlights the effect of diet-induced hypercholesterolemia with normal levels (5%) of fat on liver GAGs and other associated lipoprotein receptors. Hypercholesterolemia was induced in rats by feeding diet supplemented with 0...
July 31, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28725968/microglial-mediated-pdgf-cc-activation-increases-cerebrovascular-permeability-during-ischemic-stroke
#7
Enming Joseph Su, Chunzhang Cao, Linda Fredriksson, Ingrid Nilsson, Christina Stefanitsch, Tamara K Stevenson, Juanjuan Zhao, Margret Ragsdale, Yu-Yo Sun, Manuel Yepes, Chia-Yi Kuan, Ulf Eriksson, Dudley K Strickland, Daniel A Lawrence, Li Zhang
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα)...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28724630/altered-met-receptor-phosphorylation-and-lrp1-mediated-uptake-in-cells-lacking-carbohydrate-dependent-lysosomal-targeting
#8
Megan Aarnio-Peterson, Peng Zhao, Seok-Ho Yu, Courtney Christian, Heather Flanagan-Steet, Lance Wells, Richard Steet
Acid hydrolases utilize a carbohydrate-dependent mechanism for lysosomal targeting. These hydrolases acquire a mannose 6-phosphate tag by the action of the GlcNAc-1-phosphotransferase enzyme, allowing them to bind receptors and traffic to endosomes. Loss of GlcNAc-1-phosphotransferase results in hydrolase hypersecretion and profound lysosomal storage. Little, however, is known about how these cellular phenotypes affect the trafficking, activity and localization of surface glycoproteins. To address this question, we profiled the abundance of surface glycoproteins in WT and CRISPR-mediated GNPTAB-/- HeLa cells and identified changes in numerous glycoproteins including the uptake receptor LRP1 and multiple receptor tyrosine kinases...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28699828/glioma-targeted-delivery-strategy-of-doxorubicin-loaded-liposomes-by-dual-ligand-modification
#9
Wei Han, Guangfu Yin, Ximing Pu, Xianchun Chen, Xiaoming Liao, Zhongbing Huang
The blood-brain barrier (BBB) is the protective parclose of brain safety, but it is also the main obstacle of the drug delivery to cerebral parenchyma, which hamper therapy for brain diseases. In this work, a glioma targeted drug delivery system was developed through loading doxorubicin into Angiopep-2 and TAT peptide dual-modified liposomes (DOX-TAT-Ang-LIP). Low-density lipoprotein receptor-related protein-1 (LRP1) was one receptor overexpressed on both BBB and glioma cytomembranes. Angiopep-2, a specific ligand of LRP1, exhibited high LRP1 binding efficiency...
July 12, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28698188/a-dab2ip-genotype-sex-interaction-is-associated-with-abdominal-aortic-aneurysm-expansion
#10
Zi Ye, Erin Austin, Daniel J Schaid, Kent R Bailey, Patricia A Pellikka, Iftikhar J Kullo
A faster expansion rate of abdominal aortic aneurysm (AAA) increases the risk of rupture. Women are at higher risk of rupture than men, but the mechanisms underlying this increased risk are unknown. We investigated whether genetic variants that influence susceptibility for AAA (CDKN2A-2B, SORT1, DAB2IP, LRP1 and LDLR) are associated with AAA expansion and whether these associations differ by sex in 650 patients with AAA (mean age 70±8 years, 17% women) enrolled in the Mayo Clinic Vascular Disease Biorepository...
July 11, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28684538/tissue-type-plasminogen-activator-regulates-macrophage-activation-and-innate-immunity
#11
Elisabetta Mantuano, Pardis Azmoon, Coralie Brifault, Michael A Banki, Andrew S Gilder, Wendy M Campana, Steven L Gonias
Tissue-type plasminogen activator (tPA) is the major intravascular activator of fibrinolysis and a ligand for receptors involved in cell-signaling. In cultured macrophages, tPA inhibits the response to lipopolysaccharide (LPS) by a pathway that apparently requires LDL Receptor-related Protein-1 (LRP1). Herein, we show that the mechanism by which tPA neutralizes LPS involves rapid reversal of IκBα phosphorylation. tPA independently induced transient IκBα phosphorylation and ERK1/2 activation in macrophages; however, these events that did not trigger inflammatory mediator expression...
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28669880/role-of-vitamin-d-in-amyloid-clearance-via-lrp-1-upregulation-in-alzheimer-s-disease-a-potential-therapeutic-target
#12
REVIEW
Parmi Patel, Jigna Shah
Amyloid beta (Aβ) deposition is considered to be one of the primary reason to trigger Alzheimer's disease (AD). Literature clearly suggests decline in Aβ clearance to be accountable for progression of late onset AD as compared to augmented Aβ production. There may be several pathways for Aβ clearance out of which one of the major pathway is the vascular-mediated removal of Aβ from the brain across the blood-brain barrier (BBB) via efflux pumps or receptors. Among Aβ scavenger receptors, low density lipoprotein receptor related protein (LRP-1) has been most extensively studied...
June 30, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28668966/long-non-coding-rna-malat1-decreases-the-sensitivity-of-resistant-glioblastoma-cell-lines-to-temozolomide
#13
Hongwei Li, Xiaoli Yuan, Dongming Yan, Dongpeng Li, Fangxia Guan, Yang Dong, Hao Wang, Xianzhi Liu, Bo Yang
BACKGROUND/AIM: Multidrug resistance (MDR) is largely responsible for the failure of chemotherapy. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript (MALAT1) has been reported to be closely related to tumor biology. In the present study, whether MALAT1 contributes to the resistance of glioblastoma cell lines to temozolomide (TMZ) was investigated. METHODS: The glioblastoma cell lines U251 and U87 were exposed to increasing concentrations of TMZ to generate TMZ-resistant colonies (the U251/TMZ and U87/TMZ cell lines)...
July 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28662213/verification-and-characterization-of-an-alternative-low-density-lipoprotein-receptor-related-protein-1-splice-variant
#14
Marlen Kolb, Susanne Kurz, Angelika Schäfer, Klaus Huse, Andreas Dietz, Gunnar Wichmann, Gerd Birkenmeier
BACKGROUND: Low density lipoprotein (LDL) receptor-related protein 1 (LRP1) is a ubiquitously expressed multi-ligand endocytosis receptor implicated in a wide range of signalling, among others in tumour biology. Tumour-associated genomic mutations of the LRP1 gene are described, but nothing is known about cancer-associated expression of LRP1 splice variants Therefore, the focus of this study was on an annotated truncated LRP1 splice variant (BC072015.1; NCBI GenBank), referred to as smLRP1, which was initially identified in prostate and lung carcinoma...
2017: PloS One
https://www.readbyqxmd.com/read/28656081/effect-of-rosiglitazone-on-amyloid-precursor-protein-processing-and-a%C3%AE-clearance-in-streptozotocin-induced-rat-model-of-alzheimer-s-disease
#15
Li Wang, Wei Liu, Ying Fan, Tingting Liu, Chunjiang Yu
OBJECTIVES: Increasing evidence suggests that Alzheimer's disease (AD) is associated with diabetes. Rosiglitazone, a peroxisome proliferator-activated receptor γ (PPAR-γ) agonist and anti-diabetic agent, may improve symptoms of AD. However, the underlying therapeutic potential of it has not been fully elucidated. MATERIALS AND METHODS: Rats were divided into four groups: control group, sham operated group, Streptozotocin (STZ) group, rosiglitazone (RGZ) group...
May 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28623956/differential-protein-expression-in-chicken-macrophages-and-heterophils-in-vivo-following-infection-with-salmonella-enteritidis
#16
Zuzana Sekelova, Hana Stepanova, Ondrej Polansky, Karolina Varmuzova, Marcela Faldynova, Radek Fedr, Ivan Rychlik, Lenka Vlasatikova
In this study we compared the proteomes of macrophages and heterophils isolated from the spleen 4 days after intravenous infection of chickens with Salmonella Enteritidis. Heterophils were characterized by expression of MMP9, MRP126, LECT2, CATHL1, CATHL2, CATHL3, LYG2, LYZ and RSFR. Macrophages specifically expressed receptor proteins, e.g. MRC1L, LRP1, LGALS1, LRPAP1 and a DMBT1L. Following infection, heterophils decreased ALB and FN1, and released MMP9 to enable their translocation to the site of infection...
June 17, 2017: Veterinary Research
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
#17
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/28596374/lrp1-dependent-bmper-signaling-regulates-lipopolysaccharide-induced-vascular-inflammation
#18
Pamela Lockyer, Hua Mao, Qiying Fan, Luge Li, Li-Yuan Yu-Lee, N Tony Eissa, Cam Patterson, Liang Xie, Xinchun Pi
OBJECTIVE: Bacterial endotoxin (lipopolysaccharide)-mediated sepsis involves dysregulated systemic inflammation, which injures the lung and other organs, often fatally. Vascular endothelial cells act as both targets and mediators of lipopolysaccharide-induced inflammatory responses. Dysfunction of endothelium results in increases of proinflammatory cytokine production and permeability leakage. BMPER (bone morphogenetic protein-binding endothelial regulator), an extracellular modulator of bone morphogenetic protein signaling, has been identified as a vital component in chronic endothelial inflammatory responses and atherosclerosis...
August 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28589128/low-density-lipoprotein-receptor-related-protein-1-signaling-in-angiogenesis
#19
REVIEW
Hua Mao, Liang Xie, Xinchun Pi
Low-density lipoprotein receptor-related protein-1 (LRP1) plays multifunctional roles in lipid homeostasis, signaling transduction, and endocytosis. It has been recognized as an endocytic receptor for many ligands and is involved in the signaling pathways of many growth factors or cytokines. Dysregulation of LRP1-dependent signaling events contributes to the development of pathophysiologic processes such as Alzheimer's disease, atherosclerosis, inflammation, and coagulation. Interestingly, recent studies have linked LRP1 with endothelial function and angiogenesis, which has been underappreciated for a long time...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28588032/inactivation-of-%C3%AE-secretases-leads-to-accumulation-of-substrates-and-non-alzheimer-neurodegeneration
#20
Hermien Acx, Lutgarde Serneels, Enrico Radaelli, Serge Muyldermans, Cécile Vincke, Elise Pepermans, Ulrike Müller, Lucía Chávez-Gutiérrez, Bart De Strooper
γ-Secretases are a family of intramembrane cleaving aspartyl proteases and important drug targets in Alzheimer's disease. Here, we generated mice deficient for all γ-secretases in the pyramidal neurons of the postnatal forebrain by deleting the three anterior pharynx defective 1 (Aph1) subunits (Aph1abc cKO Cre(+)). The mice show progressive cortical atrophy, neuronal loss, and gliosis. Interestingly, this is associated with more than 10-fold accumulation of membrane-bound fragments of App, Aplp1, Nrg1, and Dcc, while other known substrates of γ-secretase such as Aplp2, Lrp1, and Sdc3 accumulate to lesser extents...
August 2017: EMBO Molecular Medicine
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