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https://www.readbyqxmd.com/read/28533442/the-role-of-shed-prp-c-in-the-neuropathogenesis-of-hiv-infection
#1
Bezawit W Megra, Eliseo A Eugenin, Joan W Berman
HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40-70% of HIV-infected people. The nonpathogenic cellular isoform of the human prion protein (PrP(c)) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrP(c) (sPrP(c)) is increased in the cerebrospinal fluid of HIV-infected people with cognitive deficits as compared with infected people with no impairment. In this article, we demonstrate that CCL2 and TNF-α, inflammatory mediators that are elevated in the CNS of HIV-infected people, increase shedding of PrP(c) from human astrocytes by increasing the active form of the metalloprotease ADAM10...
May 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526588/adam10-and-%C3%AE-secretase-regulate-sensory-regeneration-in-the-avian-vestibular-organs
#2
Mark E Warchol, Jennifer Stone, Matthew Barton, Jeffrey Ku, Rose Veile, Nicolas Daudet, Michael Lovett
The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability...
May 16, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28505974/state-of-play-in-alzheimer-s-disease-genetics
#3
Jin-Bao Zhu, Chen-Chen Tan, Lan Tan, Jin-Tai Yu
Alzheimer's disease (AD), the main form of dementia in the elderly, is the most common progressive neurodegenerative disease characterized by rapidly progressive cognitive dysfunction and behavior impairment. AD exhibits a considerable heritability and great advances have been made in approaches to searching the genetic etiology of AD. In AD genetic studies, methods have developed from classic linkage-based and candidate-gene-based association studies to genome-wide association studies (GWAS) and next generation sequencing...
May 11, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28505155/oxidative-stress-and-expression-of-insulin-signaling-proteins-in-the-brain-of-diabetic-rats-role-of-nigella-sativa-oil-and-antidiabetic-drugs
#4
Mahmoud Balbaa, Shaymaa A Abdulmalek, Sofia Khalil
BACKGROUND AND OBJECTIVES: Insulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer's progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated...
2017: PloS One
https://www.readbyqxmd.com/read/28496400/lrp1-modulates-app-intraneuronal-transport-and-processing-in-its-monomeric-and-dimeric-state
#5
Uta-Mareike Herr, Paul Strecker, Steffen E Storck, Carolin Thomas, Verena Rabiej, Anne Junker, Sandra Schilling, Nadine Schmidt, C Marie Dowds, Simone Eggert, Claus U Pietrzik, Stefan Kins
The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP and affects its processing. This is assumed to be mostly caused by the impact of LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early in the secretory pathway was reported whereat retention of LRP1 in the ER leads to decreased APP cell surface levels and in turn, to reduced Aβ secretion. Here, we extended the biochemical and immunocytochemical analyses by showing via live cell imaging analyses in primary neurons that LRP1 and APP are transported only partly in common (one third) but to a higher degree in distinct fast axonal transport vesicles...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28484521/urinary-podocyte-associated-mrna-levels-correlate-with-proximal-tubule-dysfunction-in-early-diabetic-nephropathy-of-type-2-diabetes-mellitus
#6
Ligia Petrica, Sorin Ursoniu, Florica Gadalean, Adrian Vlad, Gheorghe Gluhovschi, Victor Dumitrascu, Daliborca Vlad, Cristina Gluhovschi, Silvia Velciov, Flaviu Bob, Petru Matusz, Oana Milas, Alina Secara, Anca Simulescu, Roxana Popescu
AIM: The study assessed mRNA expression of podocyte-associated molecules in urinary sediments of patients with type 2 diabetes mellitus (DM) in relation to urinary podocytes, biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. METHODS: A total of 76 patients with type 2 DM and 20 healthy subjects were enrolled in a cross-sectional study, and assessed concerning urinary podocytes, urinary mRNA of podocyte-associated genes, urinary biomarkers of podocyte damage and of PT dysfunction...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28473446/human-plasma-thioredoxin-80-increases-with-age-and-in-apoe-mice-induces-inflammation-angiogenesis-and-atherosclerosis
#7
Dominique Couchie, Boris Vaisman, Amna Abderrazak, Dler Faieeq Darweesh Mahmood, Magda M Hamza, Fanny Canesi, Vimala Diderot, Khadija El Hadri, Anne E Nègre-Salvayre, Aurélie Le Page, Tamas Fulop, Alan T Remaley, Mustapha Rouis
Background -Thioredoxin-1 (TRX1), a ubiquitous 12 kDa protein, exerts anti-oxidant and anti-inflammatory effects. In contrast, the truncated form, called TRX80, produced by macrophages induces up-regulation of pro-inflammatory cytokines. TRX80 also promotes the differentiation of mouse peritoneal and human macrophages toward a pro-inflammatory M1 phenotype. Methods -TRX1 and TRX80 plasma levels were determined using specific ELISA. ADAM-17 and ADAM-10 activities were measured using respectively SensoLyte® 520 ADAM10 Activity Assay Kit *Fluorimetric* and InnoZyme™ TACE Activity Kit...
May 4, 2017: Circulation
https://www.readbyqxmd.com/read/28455519/calcium-sensing-receptor-antagonist-nps-2143-restores-amyloid-precursor-protein-physiological-non-amyloidogenic-processing-in-a%C3%AE-exposed-adult-human-astrocytes
#8
Anna Chiarini, Ubaldo Armato, Daisong Liu, Ilaria Dal Prà
Physiological non-amyloidogenic processing (NAP) of amyloid precursor holoprotein (hAPP) by α-secretases (e.g., ADAM10) extracellularly sheds neurotrophic/neuroprotective soluble (s)APPα and precludes amyloid-β peptides (Aβs) production via β-secretase amyloidogenic processing (AP). Evidence exists that Aβs interact with calcium-sensing receptors (CaSRs) in human astrocytes and neurons, driving the overrelease of toxic Aβ42/Aβ42-os (oligomers), which is completely blocked by CaSR antagonist (calcilytic) NPS 2143...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28455399/drug-blocks-synaptic-hijacking-in-gliomas
#9
(no author information available yet)
An enzyme called ADAM10 cleaves a protein found in synaptic membranes, creating a soluble factor that can fuel the growth of brain tumors. Blocking this enzyme shrinks tumors in xenograft models of pediatric glioblastoma and diffuse intrinsic pontine glioma, two brain cancers with few to no effective drug options, researchers reported at the American Academy of Neurology 2017 Annual Meeting.
April 28, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28454261/clinical-significance-of-adam10-expression-in-laryngeal-carcinoma
#10
Bo You, Miao Gu, Xiaolei Cao, Xingyu Li, Si Shi, Ying Shan, Yiwen You
Recent findings suggest that upregulated a disintegrin and metalloproteinase (ADAM)10 expression participates in the progression of multiple types of cancer. However, the expression pattern and clinicopathological significance of ADAM10, and its potential prognostic role in laryngeal carcinoma remains to be explored. The present study firstly determined the significantly elevated expression status of ADAM10 protein and messenger RNA in laryngeal carcinoma tissues compared with that in adjacent non-tumor tissues by western blotting and reverse transcription-quantitative polymerase chain reaction analysis...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28449222/tspan33-is-expressed-in-transitional-and-memory-b-cells-but-is-not-responsible-for-high-adam10-expression
#11
César Augusto Pérez-Martínez, José Luis Maravillas-Montero, Iván Meza-Herrera, Felipe Vences-Catalán, Albert Zlotnik, Leopoldo Santos-Argumedo
Tetraspanins are a family of transmembrane proteins that form membrane microdomains. They play important roles in migration, adhesion, and other cellular processes. TspanC8, a subfamily of tetraspanins, were found to associate and promote ADAM10 trafficking and cell surface localization. One of its members, Tspan33, is expressed in activated B cells. Using RT-PCR and flow cytometry, we analyzed the pattern of expression of Tspan33 in B cells from healthy donors. We found Tspan33 expression in early and late stages of B cell development...
April 27, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28442704/discovery-of-an-enzyme-and-substrate-selective-inhibitor-of-adam10-using-an-exosite-binding-glycosylated-substrate
#12
Franck Madoux, Daniela Dreymuller, Jean-Phillipe Pettiloud, Radleigh Santos, Christoph Becker-Pauly, Andreas Ludwig, Gregg B Fields, Thomas Bannister, Timothy P Spicer, Mare Cudic, Louis D Scampavia, Dmitriy Minond
ADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10 and ADAM17 inhibitor development has been focused on the discovery of compounds that bind the active site zinc, however, in recent years, there has been a shift from active site to secondary substrate binding site (exosite) inhibitor discovery in order to identify non-zinc-binding molecules. In the present work a glycosylated, exosite-binding substrate of ADAM10 and ADAM17 was utilized to screen 370,276 compounds from the MLPCN collection...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28437250/ionizing-radiation-reduces-adam10-expression-in-brain-microvascular-endothelial-cells-undergoing-stress-induced-senescence
#13
Lucinda S McRobb, Matthew J McKay, Jennifer R Gamble, Michael Grace, Vaughan Moutrie, Estevam D Santos, Vivienne S Lee, Zhenjun Zhao, Mark P Molloy, Marcus A Stoodley
Cellular senescence is associated with aging and is considered a potential contributor to age-associated neurodegenerative disease. Exposure to ionizing radiation increases the risk of developing premature neurovascular degeneration and dementia but also induces premature senescence. As cells of the cerebrovascular endothelium are particularly susceptible to radiation and play an important role in brain homeostasis, we investigated radiation-induced senescence in brain microvascular endothelial cells (EC). Using biotinylation to label surface proteins, streptavidin enrichment and proteomic analysis, we analyzed the surface proteome of stress-induced senescent EC in culture...
April 2017: Aging
https://www.readbyqxmd.com/read/28428248/new-insights-into-the-tetraspanin-tspan5-using-novel-monoclonal-antibodies
#14
Julien Saint-Pol, Martine Billard, Emmanuel Dornier, Etienne Eschenbrenner, Lydia Danglot, Claude Boucheix, Stéphanie Charrin, Eric Rubinstein
Tspan5 is a member of a subgroup of tetraspanins referred to as TspanC8. These tetraspanins directly interact with the metalloprotease ADAM10, regulate its exit from the endoplasmic reticulum and subsequent trafficking, and differentially regulate its ability to cleave various substrates and activate Notch signaling. The study of Tspan5 has been limited by the lack of good antibodies. This study provides new insights into Tspan5 using new monoclonal antibodies (mAbs), including two mAbs recognizing both Tspan5 and the highly similar tetraspanin Tspan17...
April 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28427048/1-25-dihydroxyvitamin-d3-attenuates-the-effects-of-lipopolysaccharide-by-causing-adam10-dependent-ectodomain-shedding-of-toll-like-receptor-4
#15
Won Seok Yang, Jin Ju Kim, Nam Jeong Han, Eun Kyoung Lee, Su-Kil Park
BACKGROUND/AIMS: We investigated how 1,25-dihydroxyvitamin D3 (1,25D3) inhibits the effects of lipopolysaccharide (LPS) in human aortic endothelial cells. METHODS: Cellular signaling was explored by determination of protein abundance with Western blot, measurement of cytosolic Ca2+ concentration and immunofluorescence staining for a disintegrin and metalloprotease 10 (ADAM10). RESULTS: LPS stimulated the expression of intercellular adhesion molecule 1 (ICAM-1) through toll-like receptor 4 (TLR4) and subsequent activation of p38 mitogen-activated protein kinase (p38 MAPK)...
April 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28413720/direct-imaging-of-app-proteolysis-in-living-cells
#16
Niccoló Parenti, Ambra Del Grosso, Claudia Antoni, Marco Cecchini, Renato Corradetti, Francesco S Pavone, Martino Calamai
Alzheimer's disease is a multifactorial disorder caused by the interaction of genetic, epigenetic and environmental factors. The formation of cytotoxic oligomers consisting of Aβ peptide is widely accepted as being one of the main key events triggering the development of Alzheimer's disease. Aβ peptide production results from the specific proteolytic processing of the amyloid precursor protein (APP). Deciphering the factors governing the activity of the secretases responsible for the cleavage of APP is still a critical issue...
2017: PeerJ
https://www.readbyqxmd.com/read/28413487/vandetanib-and-adam-inhibitors-synergistically-attenuate-the-pathological-migration-of-ebv-infected-retinal-pigment-epithelial-cells-by-regulating-the-vegf-mediated-mapk-pathway
#17
Daejin Kim, Hyun-Suk Ko, Ga Bin Park, Dae Young Hur, Yeong Seok Kim, Jae Wook Yang
The extracellular signals induced by vascular endothelial growth factor (VEGF) are implicated in choroidal neovascularization (CNV) and thus, are associated with vision-limiting complications in the human retina. Vandetanib is an oral anticancer drug that selectively inhibits the activities of VEGF receptor and epidermal growth factor receptor tyrosine kinase; however, the effects of vandetanib on VEGF in retinal pigment epithelial (RPE) cells have not yet been studied. In the present study, a combined treatment of vandetanib and a disintegrin and metalloproteinase (ADAM) protein inhibitors were used to assess the regulation of Epstein-Barr virus (EBV)-infected ARPE19 cells (ARPE19/EBV) migration as a model of CNV...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28409746/the-role-of-adam10-in-alzheimer-s-disease
#18
Xiang-Zhen Yuan, Sen Sun, Chen-Chen Tan, Jin-Tai Yu, Lan Tan
As a member of the A Disintegrin And Metalloproteinase (ADAM) family, ADAM10 has been identified as the constitutive α-secretase in the process of amyloid-β protein precursor (AβPP) cleavage and plays a critical role in reducing the generation of the amyloid-β (Aβ) peptides. Recent studies have demonstrated its beneficial role in alleviating the pathologic impairment in Alzheimer's disease (AD) both in vitro and in vivo. However, the role of ADAM10 in AD and the underlying molecular mechanisms are still not well established...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28409157/ferulic-acid-suppresses-amyloid-%C3%AE-production-in-the-human-lens-epithelial-cell-stimulated-with-hydrogen-peroxide
#19
Noriaki Nagai, Sachiyo Kotani, Yu Mano, Akina Ueno, Yoshimasa Ito, Toshio Kitaba, Takumi Takata, Noriko Fujii
It is well known that oxidative stresses induce the production of amyloid β (Aβ) in the brain, lens, and retina, leading to age-related diseases. In the present study, we investigated the effects of ferulic acid on the Aβ levels in H2O2-stimulated human lens epithelial (HLE) SRA 01/04 cells. Three types of Aβ peptides (Aβ1-40, Aβ1-42, and Aβ1-43) were measured by ELISA, and the levels of mRNA for the expressed proteins related to Aβ production (APP, BACE1, and PS proteins) and degradation (ADAM10, NEP, and ECE1 proteins) were determined by quantitative real-time RT-PCR...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28408220/first-insight-into-structure-activity-relationships-of-selective-meprin-%C3%AE-inhibitors
#20
Daniel Ramsbeck, Antje Hamann, Dagmar Schlenzig, Stephan Schilling, Mirko Buchholz
The astacin proteases meprin α and β are emerging drug targets for treatment of disorders such as kidney failure, fibrosis or inflammatory bowel disease. However, there are only few inhibitors of both proteases reported to date. Starting from NNGH as lead structure, a detailed elaboration of the structure-activity relationship of meprin β inhibitors was performed, leading to compounds with activities in the lower nanomolar range. Considering the preference of meprin β for acidic residues in the P1' position, the compounds were optimized...
April 5, 2017: Bioorganic & Medicinal Chemistry Letters
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