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Héctor F Araya, Hugo Sepulveda, Carlos O Lizama, Oscar A Vega, Sofia Jerez, Pedro F Briceño, Roman Thaler, Scott M Riester, Marcelo Antonelli, Flavio Salazar-Onfray, Juan Pablo Rodríguez, Ricardo D Moreno, Martin Montecino, Martine Charbonneau, Claire M Dubois, Gary S Stein, Andre J van Wijnen, Mario A Galindo
Osteoblast differentiation is controlled by transcription factor RUNX2 which temporally activates or represses several bone-related genes, including those encoding extracellular matrix proteins or factors that control cell-cell, and cell-matrix interactions. Cell-cell communication in the many skeletal pericellular micro-niches is critical for bone development and involves paracrine secretion of growth factors and morphogens. This paracrine signaling is in part regulated by "A Disintegrin And Metalloproteinase" (ADAM) proteins...
June 19, 2018: Journal of Cellular Biochemistry
Young-Jung Kim, Ji-Young Yoo, Ok-Soon Kim, Han-Byeol Kim, Junghwa Ryu, Hye-Sun Kim, Jun-Ho Lee, Hong-Il Yoo, Dae-Yong Song, Tai-Kyoung Baik, Ran-Sook Woo
The amyloid precursor protein (APP) is a key molecule in Alzheimer's disease. The prevailing view is that APP is initially transported to the plasma membrane as a full-length protein. Its localization at the cell surface can trigger downstream signaling and APP cleavage. Our previous work has shown that Neuregulin 1 (NRG1) has neuroprotective effects in an Alzheimer's disease model. In the present study, we examine whether NRG1 signaling is involved in APP expression and non-amyloidogenic processing in neuronal cells...
May 29, 2018: Journal of Pharmacological Sciences
Olga Stasikowska-Kanicka, Małgorzata Wągrowska-Danilewicz, Paulina Kulicka, Marian Danilewicz
ADAMs (a disintegrin and metalloproteinase) are important mediators of cell signalling events, which play a role in the pathogenesis and progression of cancers. Immunohistochemical method was used to examine the immunoexpression of ADAM10 and microvessel density in 80 cases of oral squamous cell carcinoma (OSCC): without metastases - OSCC M(-) (n = 38), and with metastases - OSCC M(+) (n = 42), in 24 cases of oral leukoplakia (OLK), (15 cases with low-grade dysplasia - OLK-LG, and 9 cases with high-grade dysplasia - OLK-HG), and 19 controls...
2018: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
Aritoshi Ri, Man Hagiyama, Takao Inoue, Azusa Yoneshige, Ryuichiro Kimura, Yoshinori Murakami, Akihiko Ito
Pulmonary emphysema usually arises in cigarette smokers, and often progresses after smoking cessation and even in ex-smokers. Lung-epithelial cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is extracellularly shed to produce a proapoptotic C-terminal fragment (CTF) within the cell and contribute to the development of emphysema. Here, we made an ex-smoker model using C57BL/6 mice; mice (6-week-old; 5 mice per group) were exposed to passive smoke of eight cigarettes twice a day 5 days a week until 18 weeks of age, and were then left untreated until 30 weeks of age...
2018: Frontiers in Cell and Developmental Biology
Vedanta Mehta, Laura Fields, Ian M Evans, Maiko Yamaji, Caroline Pellet-Many, Timothy Jones, Marwa Mahmoud, Ian Zachary
OBJECTIVE: NRP1(neuropilin-1) acts as a coreceptor for VEGF (vascular endothelial growth factor) with an essential role in angiogenesis. Recent findings suggest that posttranslational proteolytic cleavage of VEGF receptors may be an important mechanism for regulating angiogenesis, but the role of NRP1 proteolysis and the NRP1 species generated by cleavage in endothelial cells is not known. To characterize NRP1 proteolytic cleavage in endothelial cells, determine the mechanism, and investigate the role of NRP1 cleavage in regulation of endothelial cell function...
June 7, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Emiel P C van der Vorst, Christian Weber, Marjo M P C Donners
A disintegrin and metalloproteases (ADAMs) are membrane-bound enzymes responsible for the shedding or cleavage of various cell surface molecules, such as adhesion molecules, cytokines/chemokines and growth factors. This shedding can result in the release of soluble proteins that can exert agonistic or antagonistic functions. Additionally, ADAM-mediated cleavage can render these membrane proteins inactive. This review will describe the role and association of ADAMs in various pathologies with a main focus on ADAM10 and ADAM17 in atherosclerosis, including a brief overview of atherosclerosis-related ADAM substrates...
June 6, 2018: Thrombosis and Haemostasis
Jessyka Maria de França Bram, Leda Leme Talib, Helena Passarelli Giroud Joaquim, Tamires Alves Sarno, Wagner Farid Gattaz, Orestes Vicente Forlenza
The clinical diagnosis of Alzheimer's disease (AD) is a probabilistic formulation that may lack accuracy particularly at early stages of the dementing process. Abnormalities in amyloid-beta precursor protein (APP) metabolism and in the level of APP secretases have been demonstrated in platelets, and to a lesser extent in leukocytes, of AD patients, with conflicting results. The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls...
May 29, 2018: European Archives of Psychiatry and Clinical Neuroscience
Oluwatomi Akingbade, Claire Gibson, Raj N Kalaria, Elizabeta B Mukaetova-Ladinska
Dementia continues to be the most burdening neurocognitive disorder, having a negative impact on the lives of millions. The search for biomarkers to improve the clinical diagnosis of dementia is ongoing, with the focus on effective use of readily accessible peripheral markers. In this review, we concentrate on platelets as biomarkers of dementia and analyze their potential as easily-accessible clinical biomarkers for various subtypes of dementia. Current platelet protein biomarkers that have been investigated for their clinical utility in the diagnosis of dementia, in particular Alzheimer's disease, include amyloid-β protein precursor (AβPP), the AβPP secretases (BACE1 and ADAM10), α-synuclein, tau protein, serotonin, and cholesterol, phospholipases, clusterin, IgG, surface receptors, MAO-B, and coated platelets...
May 19, 2018: Journal of Alzheimer's Disease: JAD
Riccardo E Marioni, Sarah E Harris, Qian Zhang, Allan F McRae, Saskia P Hagenaars, W David Hill, Gail Davies, Craig W Ritchie, Catharine R Gale, John M Starr, Alison M Goate, David J Porteous, Jian Yang, Kathryn L Evans, Ian J Deary, Naomi R Wray, Peter M Visscher
Alzheimer's disease (AD) is a public health priority for the 21st century. Risk reduction currently revolves around lifestyle changes with much research trying to elucidate the biological underpinnings. We show that self-report of parental history of Alzheimer's dementia for case ascertainment in a genome-wide association study of 314,278 participants from UK Biobank (27,696 maternal cases, 14,338 paternal cases) is a valid proxy for an AD genetic study. After meta-analysing with published consortium data (n = 74,046 with 25,580 cases across the discovery and replication analyses), three new AD-associated loci (P < 5 × 10-8 ) are identified...
May 18, 2018: Translational Psychiatry
Francesca Tosetti, Roberta Venè, Caterina Camodeca, Elisa Nuti, Armando Rossello, Cristina D'Arrigo, Denise Galante, Nicoletta Ferrari, Alessandro Poggi, Maria Raffaella Zocchi
Shedding of ADAM10 substrates, like TNFα, MICA or CD30, is reported to affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. Soluble forms of these molecules and ADAM10 can be carried and spread in the microenvironment by exosomes released by tumor cells. We reported new ADAM10 inhibitors able to prevent MICA shedding in Hodgkin lymphoma (HL), leading to recognition of HL cells by cytotoxic lymphocytes. In this paper, we show that the mature bioactive form of ADAM10 is released in exosome-like vesicles (ExoV) by HL cells and lymph node mesenchymal stromal cells (MSC)...
2018: Oncoimmunology
Kaku Goto, Jun Arai, Anthony Stephanou, Naoya Kato
Our previous genome-wide association study identified the anti-tumor ligand MHC class I polypeptide-related sequence A ( MICA ) as a susceptibility gene for hepatitis C virus-induced hepatocellular carcinoma (HCC). We subsequently proved that pharmacological restoration of membrane-bound MICA in HCC cells boosted natural killer cell-mediated anti-cancer effects, confirming that a MICA sheddase, a disintegrin and metalloproteinase 10 (ADAM10), is a therapeutic target. We here searched for approved drugs with inhibitory effects on ADAM10 in vitro , and the anti-alcoholism agent, disulfiram, was identified...
April 10, 2018: Oncotarget
Zhuo Wang, Ya-Hong Zhang, Wei Zhang, Hui-Ling Gao, Man-Li Zhong, Ting-Ting Huang, Rui-Fang Guo, Na-Na Liu, Dan-Dan Li, Yin Li, Zhan-You Wang, Pu Zhao
Copper is essential for the generation of reactive oxygen species (ROS), which are induced by amyloid-β (Aβ) aggregation; thus, the homeostasis of copper is believed to be a therapeutic target for Alzheimer's disease (AD). Although clinical trials of copper chelators show promise when applied in AD, the underlying mechanism is not fully understood. Here, we reported that copper chelators promoted nonamyloidogenic processing of AβPP through MT1/2 /CREB-dependent signaling pathways. First, we found that the formation of Aβ plaques in the cortex was significantly reduced, and learning deficits were significantly improved in AβPP/PS1 transgenic mice by copper chelator tetrathiomolybdate (TM) administration...
April 30, 2018: Journal of Pineal Research
Hongwei Guo, Deyu Xia, Shaohua Liao, Bing Niu, Jigang Tang, Huaiqiang Hu, Hairong Qian, Bingzhen Cao
Alzheimer's disease (AD) is primarily characterized by the production and deposit of β-amyloid protein (Aβ) in β-amyloid plaques (APs). On this basis, we investigated whether vascular endothelial growth factor (VEGF), a growth factor with important neuroprotective activity, may provide a therapeutic opportunity for treating AD. We initially found that the expression and production of VEGF was downregulated in the brains of Tg2576 mice during the course of AD development and progression. Restoring VEGF in the brains of Tg2576 mice antagonized the production and deposit of Aβ in Tg2576 mice...
April 24, 2018: Neuroscience Research
Il-Young Hwang, Cedric Boularan, Kathleen Harrison, John H Kehrl
The follicular (FO) versus marginal zone (MZ) B cell fate decision in the spleen depends upon BCR, BAFF, and Notch2 signaling. Whether or how Gi signaling affects this fate decision is unknown. Here, we show that direct contact with Notch ligand expressing stromal cells (OP9-Delta-like 1) cannot promote normal MZ B cell development when progenitor B cells lack Gαi proteins, or if Gi signaling is disabled. Consistent with faulty ADAM10-dependent Notch2 processing, Gαi -deficient transitional B cells had low ADAM10 membrane expression levels and reduced Notch2 target gene expression...
2018: Frontiers in Immunology
Jialong Guo, Juan Du, Dan Fei, Jie Xing, Jinxiang Liu, Honghua Lu
miR‑152 has been reported to be downregulated in rheumatoid arthritis (RA). However, the functional significance and molecular mechanisms underlying the role of miR‑152 in RA remain largely unknown. The present study aimed to explore the functional role and the underlying mechanisms of miR‑152 in RA. The expression of miR‑152 in serum, synovial tissues, and fibroblast‑like synoviocytes (FLS) from patients with RA and healthy controls was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
July 2018: International Journal of Molecular Medicine
Hui Yang, Hongcai Wang, Yongwei Shu, Xuling Li
miR-103 has been reported to be decreased in brain of transgenic mouse model of Alzheimer's disease (AD) and in cerebrospinal fluid (CSF) of AD patients, while the detailed mechanism of its effect on AD is obscure, thus this study aimed to investigate the effect of miR-103 expression on neurite outgrowth and cells apoptosis as well as its targets in cellular models of AD. Blank mimic (NC1-mimic), miR-103 mimic, blank inhibitor (NC2-mimic) and miR-103 inhibitor plasmids were transferred into PC12 cellular AD model and Cellular AD model of cerebral cortex neurons which were established by Aβ1-42 insult...
2018: Frontiers in Cellular Neuroscience
Luise Linsenmeier, Behnam Mohammadi, Sebastian Wetzel, Berta Puig, Walker S Jackson, Alexander Hartmann, Keiji Uchiyama, Suehiro Sakaguchi, Kristina Endres, Jörg Tatzelt, Paul Saftig, Markus Glatzel, Hermann C Altmeppen
Background: Proteolytic processing of the prion protein (PrP<superscript>C</superscript>) by endogenous proteases generates bioactive membrane-bound and soluble fragments which may help to explain the pleiotropic roles of this protein in the nervous system and in brain diseases. Shedding of almost full-length PrP<superscript>C</superscript> into the extracellular space by the metalloprotease ADAM10 is of peculiar relevance since soluble PrP stimulates axonal outgrowth and is protective in neurodegenerative conditions such as Alzheimer’s and prion disease...
April 6, 2018: Molecular Neurodegeneration
Zhuo Wang, Xueshi Huang, Pu Zhao, Limei Zhao, Zhan-You Wang
Amyloid-β (Aβ) peptides play a crucial role in the pathogenesis of Alzheimer's disease (AD), due to its neurotoxicity. Thus, blocking Aβ generation and aggregation in the brain has been realized as an efficient way for the prevention of AD. The natural product catalpol, isolated from Rehmannia glutinosa , has shown neuroprotective activities through inhibiting soluble Aβ production, degrading Aβ peptide, and attenuating Aβ toxicity and neuroinflammatory responses. In the present study, we aimed to evaluate whether catalpol reduce Aβ generation associated with regulating amyloid precursor protein (APP) proteolytic processing...
2018: Frontiers in Aging Neuroscience
Dolors Puigoriol-Illamola, Christian Griñán-Ferré, Foteini Vasilopoulou, Rosana Leiva, Santiago Vázquez, Mercè Pallàs
Elevated glucocorticoid (GC) exposure is widely accepted as a key factor in the age-related cognitive decline in rodents and humans. 11β-HSD1 is a key enzyme in the GCs pathway, catalyzing the conversion of 11β-dehydrocorticosterone to corticosterone in mice, with possible implications in neurodegenerative processes and cognitive impairment. Here, we determined the effect of a new 11β-HSD1 inhibitor, RL-118, administered to 12-month-old senescence-accelerated mouse-prone 8 (SAMP8) mice with neuropathological AD-like hallmarks and widely used as a rodent model of cognitive dysfunction...
April 2, 2018: Molecular Neurobiology
Huimin Guo, Shenghua Yang, Shaoru Li, Mengting Yan, Li Li, Hongxia Zhang
BACKGROUND: Recent studies highlight the crucial regulatory roles of long non-coding RNAs (lncRNAs) in carcinogenesis. However, involvement of the lncRNA SNHG20 in cervical cancer progression remains unclear. METHODS: The expression of SNHG20 and miR-140-5p was determined in cervical cancer. Gain or loss of function assays were used to explore the roles of SNHG20 and miR-140-5p in cervical cancer cells. Luciferase assay and Western blot were used to explore the underlying mechanisms of SNHG20 and miR-140-5p in cervical cancer progression...
June 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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