• deficiency
  • A deficiency in the levels of Cathepsin E in the body may play a part in inflammatory skin diseases such as atopic dermatitis, for which treatment would rely on fixing functionality and levels of the protein in the body. (wikipedia.org)
  • protein
  • One such protein critical for osteoclast activity is c-Src kinase, which is highly expressed in osteoclasts ( 9 , 10 ). (aacrjournals.org)
  • The size of the multinucleated assembled osteoclast allows it to focus the ion transport, protein secretory and vesicular transport capabilities of many macrophages on a localized area of bone. (wikipedia.org)
  • Cathepsin B seems to cause amyloid plaque, the root of Alzheimer's symptoms, when there are wild-type beta-secretase present in the system Overexpression of the encoded protein, which is a member of the peptidase C1 family, has been associated with esophageal adenocarcinoma and other tumors. (wikipedia.org)
  • mononuclear
  • Formation of active phosphorylated c-Src, which was highly present in osteoclast-like cells in cocultures and in peripheral blood mononuclear cell monocultures, was significantly reduced by AZD0530. (aacrjournals.org)
  • mammalian
  • Cathepsin K is the most potent mammalian collagenase. (wikipedia.org)
  • Its intracellular localization in different mammalian cells is different to that of its analog Cathepsin D. Cathepsin E associates with the membrane tissue in the intracellular canaliculi of gastric parietal cells, bile canaliculi of hepatic cells, cells of the rinal proximal tubule in the kidney, epithelial cells in the intestine, trachea and bronchi, osteoclasts and even in erythrocytes. (wikipedia.org)
  • extracellular
  • Osteoclasts lacking proteins critical for the assembly of the sealing zone cannot form a ruffled border, which is the extracellular secondary lysosome necessary for dissolving minerals and degrading bone matrix proteins ( 6 - 8 ). (aacrjournals.org)
  • inhibitor
  • Medivir has a cathepsin K inhibitor, MIV-711 (L-006235), in Phase IIa clinical trial, as a disease modifying osteoarthritis drug, as of October 2017. (wikipedia.org)
  • Pepstatin A is well known to be an inhibitor of aspartic proteinases such as pepsin, cathepsins D and E. Except for its role as a proteinase inhibitor, however, the pharmacological action of pepstatin A upon cells remain unclear. (wikipedia.org)
  • inhibition
  • Using live imaging, we observed an efficient, dose-dependent inhibition of osteoclast activity, which resulted in the maintenance of bone integrity despite an excess of osteoclast formation. (biologists.org)
  • This inhibition seems to be independent of the activities of proteinases such as cathepsin D, because the formation of osteoclasts was not suppressed with the concentration that inhibited the activity of cathepsin D. Cell signaling analysis indicated that the phosphorylation of ERK was inhibited in pepstatin A-treated cells, while the phosphorylation of IκB and Akt showed almost no change. (wikipedia.org)
  • gene
  • In addition, microarray analysis and various validation experiments comparing gene expression levels in osteoclasts from ADO II patients and healthy donors have demonstrated that ITGB5 expression is increased in the former and that PFR1, SERPINE2, and WARS expression are all decreased in ADO II osteoclasts. (springer.com)
  • aspartic
  • Along with renin and Cathepsin D, Cathepsin E is one of the only few aspartic proteases known to be made in human tissues other than those of gastrointestinal and reproductive tracts. (wikipedia.org)
  • proteins
  • These may have dozens of nuclei, and typically express major osteoclast proteins but have significant differences from cells in living bone because of the not-natural substrate. (wikipedia.org)
  • tissue
  • In response to endotoxin derived from periodontal pathogens, several osteoclast-related mediators target the destruction of alveolar bone and supporting connective tissue such as the periodontal ligament. (wikipedia.org)
  • Major drivers of this aggressive tissue destruction are matrix metalloproteinases (MMPs), cathepsins, and other osteoclast-derived enzymes. (wikipedia.org)
  • An osteoclast (from the Greek words for "bone" (ὀστέον), and "broken" (κλαστός)) is a type of bone cell that breaks down bone tissue. (wikipedia.org)
  • Cathepsin L-deficient mice were shown to have less adipose tissue, lower serum glucose and insulin levels, more insulin receptor subunits, more glucose transporter (GLUT4) and more fibronectin than wild type controls. (wikipedia.org)
  • hydrogen
  • The osteoclast releases hydrogen ions through the action of carbonic anhydrase (H2O + CO2 → HCO3− + H+) through the ruffled border into the resorptive cavity, acidifying and aiding dissolution of the mineralized bone matrix into Ca2+, H3PO4, H2CO3, water and other substances. (wikipedia.org)
  • A distinguishing factor of Cathepsin E in comparison with the structure of Cathepsin D and BACE1 can be seen at the formation of an extra hydrogen bond between the Asp 96 and Ser 99 residues, and absence of a hydrogen bond with Leu/Met at Asp 281. (wikipedia.org)
  • metastatic
  • The cathepsin A activity in lysates of metastatic lesions of malignant melanoma is significantly higher than in primary focus lysates. (wikipedia.org)
  • genetic
  • The genetic knockout for cathepsin S and K in mice with atherosclerosis was shown to reduce the size of atherosclerotic lesions. (wikipedia.org)
  • activity
  • Therefore, drugs like AZD0530, designed to inhibit Src activity, could selectively interfere with both tumor and osteoclast activity. (aacrjournals.org)
  • AZD0530 was most effective in inhibiting osteoclast-like cell formation when present at the onset of osteoclastogenesis, suggesting that Src activity is important during the initial phase of osteoclast formation. (aacrjournals.org)