Search results for "ADAM10"
showing 10 items of 61 documents
Extract of Caragana sinica as a potential therapeutic option for increasing alpha-secretase gene expression
2015
Abstract Background Alzheimer's disease represents one of the main neurological disorders in the aging population. Treatment options so far are only of symptomatic nature and efforts in developing disease modifying drugs by targeting amyloid beta peptide-generating enzymes remain fruitless in the majority of human studies. During the last years, an alternative approach emerged to target the physiological alpha-secretase ADAM10, which is not only able to prevent formation of toxic amyloid beta peptides but also provides a neuroprotective fragment of the amyloid precursor protein – sAPPalpha. Purpose To identify novel alpha-secretase enhancers from a library of 313 extracts of medicinal plant…
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…
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"
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…
Changing fate
2020
Abstract The alpha-secretase A disintegrin and metalloproteinase 10 (ADAM10) and the beta-secretase beta-APP cleaving enzyme 1 (BACE-1) compete in neurons to cleave the amyloid precursor protein (APP). The reaction started by BACE-1, designated the amyloidogenic pathway, leads to formation of neurotoxic amyloid beta peptides (A-betas), while alpha-secretase prevents this and gives rise to an alternative cleavage product (APPs-alpha, nonamyloidogenic pathway). The latter is also known to have neurotrophic and neuroprotective properties. Therefore, identification of mechanisms that lead to a switch in APP processing from the amyloidogenic to the nonamyloidogenic pathway is an attractive avenu…