Search results for "m10"
showing 10 items of 118 documents
Acitretin, an Enhancer of Alpha-Secretase Expression, Crosses the Blood-Brain Barrier and Is Not Eliminated by P-Glycoprotein
2011
<i>Background:</i> ADAM10 (a disintegrin and metalloproteinase 10) has been demonstrated to act as the main physiological α-secretase. Enzymatic activity of the α-secretase on the one hand prevents the formation of toxic Aβ peptides and on the other hand promotes the secretion of a neurotrophic and neuroprotective amyloid precursor protein fragment (APPs-α) by cleaving the amyloid precursor protein within its Aβ sequence. Enhancement of ADAM10’s gene expression may therefore present a valuable therapeutic approach for the treatment of Alzheimer’s disease (AD), where Aβ peptides are severely involved in the pathogenesis. <i>Objective:</i> In cell culture and in a tran…
Posttranslational modifications by ADAM10 shape myeloid antigen-presenting cell homeostasis in the splenic marginal zone
2021
The spleen contains phenotypically and functionally distinct conventional dendritic cell (cDC) subpopulations, termed cDC1 and cDC2, which each can be divided into several smaller and less well-characterized subsets. Despite advances in understanding the complexity of cDC ontogeny by transcriptional programming, the significance of posttranslational modifications in controlling tissue-specific cDC subset immunobiology remains elusive. Here, we identified the cell-surface–expressed A-disintegrin-and-metalloproteinase 10 (ADAM10) as an essential regulator of cDC1 and cDC2 homeostasis in the splenic marginal zone (MZ). Mice with a CD11c-specific deletion of ADAM10 (ADAM10(ΔCD11c)) exhibited a …
Oligodendrocyte precursor cells modulate the neuronal network by activity-dependent ectodomain cleavage of glial NG2.
2014
The role of glia in modulating neuronal network activity is an important question. Oligodendrocyte precursor cells (OPC) characteristically express the transmembrane proteoglycan nerve-glia antigen 2 (NG2) and are unique glial cells receiving synaptic input from neurons. The development of NG2+ OPC into myelinating oligodendrocytes has been well studied, yet the retention of a large population of synapse-bearing OPC in the adult brain poses the question as to additional functional roles of OPC in the neuronal network. Here we report that activity-dependent processing of NG2 by OPC-expressed secretases functionally regulates the neuronal network. NG2 cleavage by the α-secretase ADAM10 yields…
Induction of RAGE Shedding by Activation of G Protein-Coupled Receptors
2011
The multiligand Receptor for Advanced Glycation End products (RAGE) is involved in various pathophysiological processes, including diabetic inflammatory conditions and Alzheimers disease. Full-length RAGE, a cell surface-located type I membrane protein, can proteolytically be converted by metalloproteinases ADAM10 and MMP9 into a soluble RAGE form. Moreover, administration of recombinant soluble RAGE suppresses activation of cell surface-located RAGE by trapping RAGE ligands. Therefore stimulation of RAGE shedding might have a therapeutic value regarding inflammatory diseases. We aimed to investigate whether RAGE shedding is inducible via ligand-induced activation of G protein-coupled recep…
Up‐regulation of the α‐secretase ADAM10 by retinoic acid receptors and acitretin
2009
Late-onset Alzheimer's disease is often connected with nutritional misbalance, such as enhanced cholesterol intake, deficiency in polyunsaturated fatty acids, or hypovitaminosis. The alpha-secretase ADAM10 has been found to be regulated by retinoic acid, the bioreactive metabolite of vitamin A. Here we show that retinoids induce gene expression of ADAM10 and alpha-secretase activity by nonpermissive retinoid acid receptor/retinoid X receptor (RAR/RXR) heterodimers, whereby alpha- and beta-isotypes of RAR play a major role. However, ligands of other RXR binding partners, such as the vitamin D receptor, do not stimulate alpha-secretase activity. On the basis of these findings, we examined the…
Antecedentes y dinamismo de la ambidestreza organizativa en las pymes
2014
El objetivo de este trabajo es analizar algunos de los antecedentes de la ambidestreza organizativa en las pequenas y medianas empresas (Pymes). La ambidestreza es una capacidad dinamica que permite a las empresas obtener un elevado nivel de desempeno en situaciones que requieren alinearse con el entorno. En el trabajo se defiende que la ambidestreza tiene un componente estructural que la hace depender de los niveles previos de ambidestreza, pero que tambien tiene como antecedente las opciones de estrategia corporativa de la empresa. Concretamente, se postula que la utilizacion por parte de las empresas de las modalidades de crecimiento externo, a traves de las fusiones y adquisiciones, y d…
Autophagy Induces Expression of IL-6 in Human Periodontal Ligament Fibroblasts Under Mechanical Load and Overload and Effects Osteoclastogenesis in v…
2021
Frontiers in physiology 12, 716441 (2021). doi:10.3389/fphys.2021.716441 special issue: "Alveolar Bone: a Pivotal Role in Periodontal Disease Pathobiology and Treatment, Volume I / Fani Anagnostou, Beatriz Castaneda, Frédéric Lézot and Petros Papagerakis"
Constraining the ship contribution to the aerosol of the central Mediterranean
2017
Particulate matter with aerodynamic diameters lower than 10 µm, (PM10) aerosol samples were collected during summer 2013 within the framework of the Chemistry and Aerosol Mediterranean Experiment (ChArMEx) at two sites located north (Capo Granitola) and south (Lampedusa Island), respectively, of the main Mediterranean shipping route in the Straight of Sicily. The PM10 samples were collected with 12 h time resolutions at both sites. Selected metals, main anions, cations and elemental and organic carbon were determined. The evolution of soluble V and Ni concentrations (typical markers of heavy fuel oil combustion) was related to meteorology and ship traffic intensity in the Straight of Sicily…
Upregulation of the α-secretase ADAM10 - risk or reason for hope?
2010
A decade ago, a disintegrin and metalloproteinase 10 (ADAM10) was identified as an alpha-secretase and as a key proteinase in the processing of the amyloid precursor protein. Accordingly, the important role that it plays in Alzheimer's disease was manifested. Animal models with an overexpression of ADAM10 revealed a beneficial profile of the metalloproteinase with respect to learning and memory, plaque load and synaptogenesis. Therefore, ADAM10 presents a worthwhile target with respect to the treatment of a neurodegenerative disease such as Morbus Alzheimer. Initially, ADAM10 was suggested to be an enzyme, shaping the extracellular matrix by cleavage of collagen type IV, or to be a tumour n…
ADAM10, myelin-associated metalloendopeptidase
2013
Publisher Summary This chapter discusses the structural chemistry and the biological aspects of ADAM10. Originally, ADAM10 was characterized as a myelin-associated metalloproteinase. After cloning the bovine ADAM10 cDNA, the deduced amino acid sequence indicated that the enzyme belonged to the reprolysin subfamily and therefore was named MADM (mammalian disintegrin metalloprotease). The mammalian reprolysin subfamily has been named ADAM (a disintegrin and metalloproteinase) and MADM has been designated ADAM10. The ADAM10 homologs in Drosophila melanogaster and Caenorhabditis elegans are named kuzbanian and sup-17, respectively. The enzymatic activity of isolated ADAM10 can be monitored in v…