• protein
  • Amyloid deposition is initiated by changed of protein conformation. (biomedcentral.com)
  • Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were observed in MDMs from type 2 diabetic patients after stimulation with various danger molecules (ATP, high-mobility group protein B1, free fatty acids, islet amyloid polypeptide, and monosodium uric acid crystals). (diabetesjournals.org)
  • 2014). It is of great importance to recognize that amyloid-like protein folding is subject to stringent quality control systems. (docme.ru)
  • Yet, protein folding in ER is inefficient due to a substantial polypeptides failing to reach its native state but bringing toxic effects to the cell (Smith et al. (docme.ru)
  • Staphylococcus aureus protein α-toxin and Streptococcus pyogenes protein streptolysin O both create pores that allow unsolicited molecular transfer across membranes that disrupts vital functions. (dovepress.com)
  • They also include the action of proinflammatory cytokines, the production of reactive oxygen species, DNA fragmentation (typical of necroptosis in type 1 diabetic patients), excessive production of islet amyloid polypeptide with the consequent endoplasmic reticulum stress, disruption in autophagy mechanisms, and protein complex formation, such as the inflammasome, capable of increasing oxidative stress produced by mitochondrial damage. (hindawi.com)
  • Insulin is a polypeptide hormone formed by 51 amino acids [ 5 ] which once bound with its receptor, mainly expressed in the liver, muscular, and adipose tissue [ 6 ], and regulates a wide number of physiological processes that comprise gene mechanisms such as cellular growth and differentiation, expression of genes that code for enzymes that trigger glycogen, and lipid and protein synthesis. (hindawi.com)
  • The CALC1 gene belongs to a superfamily of related protein hormone precursors including islet amyloid precursor protein, calcitonin gene-related peptide, and the precursor of adrenomedullin. (wikipedia.org)
  • The calcitonin receptor, found on osteoclasts, and in the kidney and regions of the brain, is a G protein-coupled receptor, which is coupled by Gs to adenylate cyclase and thereby to the generation of cAMP in target cells. (wikipedia.org)
  • insulin resistance
  • Emerging evidence suggests that activation of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome leads to the maturation and secretion of interleukin (IL)-1β and is involved in the pathogenic mechanisms of obesity-induced inflammation, insulin resistance, and type 2 diabetes development ( 7 - 11 ). (diabetesjournals.org)
  • Insulin resistance per se, however, does not provoke overt diabetes as long as compensatory β-cell function is maintained. (diabetesjournals.org)
  • However, conditions that lead to sustained ER stress (i.e., prolonged and persistent insulin resistance and/or failure to reestablish proper ER homeostasis) are implicated in the deterioration of β-cell function and the development of overt diabetes ( 1 - 3 ). (diabetesjournals.org)
  • pathways
  • Identifying the cell death signalling pathways by which non-immune factors such as islet amyloid formation mediate beta-cell death in human islets during pre-transplant culture and following transplantation. (ubc.ca)
  • Among them, the activation of self-reactive lymphocytes and their infiltration in the pancreas, followed by the release of proinflammatory cytokines such as tumor necrosis factor alpha (TNF- α ), which united with its membrane receptor on the PBC, activate intracellular signaling pathways that end in the induction of proapoptotic mechanisms and, in some cases, cell death through necroptosis [ 13 , 14 ]. (hindawi.com)
  • Clinical
  • The IL-1 receptor antagonist Anakinra enhances survival and function of human islets during culture: Implications in clinical islet transplantation. (ubc.ca)
  • This study highlights that having a profound understanding in the underlying interactive mechanism between amyloid and the immune system provides research directions on the opportunities and difficulties when targeting key therapeutic points for the treatment of these devastating chronic diseases in clinical practice. (docme.ru)
  • inhibition
  • Of note, pharmacological inhibition of retrograde transport in isolated islets and insulinoma cells mimicked the phenotype of Asna1 β−/− β-cells and resulted in reduced insulin content and ER stress. (diabetesjournals.org)
  • proteins
  • HSPGs function not only as structural proteins, but also as anchors for bioactive molecules, as HS is negatively charged. (diabetesjournals.org)
  • Mechanistic studies, primarily in cell-free systems, have suggested a role for Get3 and the mammalian homolog Asna1 (also known as TRC40) in delivering tail-anchored (TA) proteins for posttranslational insertion into the ER through the CAML/WRB receptor complex ( 13 - 16 ). (diabetesjournals.org)
  • Recently, Get3/Asna1 was also shown to function, under oxidative stress conditions, as a molecular chaperone that binds unfolded proteins to prevent their irreversible aggregation ( 18 ). (diabetesjournals.org)
  • Amyloids have been known to arise from many different proteins and polypeptides. (wikipedia.org)
  • contributes
  • Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. (docme.ru)
  • oxidative stress
  • Key mechanisms of hyperglycemia-induced inflammation include nuclear factor-κB-dependent production of proinflammatory cytokines, Toll-like receptor (TLR) expression, increased oxidative stress, and inflammasome activation ( 4 , 5 ). (diabetesjournals.org)
  • In Caenorhabditis elegans , Asna1 function is required for larval growth and resistance to cisplatin, an oxidative stress-inducing anticancer drug ( 19 , 20 ). (diabetesjournals.org)
  • formation
  • Zhang Y, Jalili RB, Warnock GL, Ao Z, Marzban L , Ghahary A. Three-dimensional scaffolds reduce islet amyloid formation and enhance survival and function of cultured human islets. (ubc.ca)
  • Marzban L , Tomas A, Becker TC, Rosenberg L, Oberholzer J, Fraser PE, Halban PA, Verchere CB: siRNA-Mediated Suppression of Pro-Islet Amyloid Polypeptide Expression Inhibits Islet Amyloid Formation and Enhances Survival of Human Islets in Culture. (ubc.ca)
  • Marzban L , Rhodes CJ, Steiner DF, Haataja L, Halban PA, and Verchere CB: Impaired NH2-terminal processing of human pro-islet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death. (ubc.ca)
  • species
  • Recently this definition has come into question as some classic, amyloid species have been observed in distinctly intracellular locations. (wikipedia.org)
  • ATTR amyloid deposits from transthyretin occur not only in Transthyretin-related hereditary amyloidosis, but also in advanced cases of aging in many tissues, in many mammalian species. (wikipedia.org)
  • Survival
  • Thus, identification of key molecules and factors that ensure proper membrane trafficking and ER homeostasis, and thereby β-cell function and survival, is important to gaining insight into the etiology of T2D. (diabetesjournals.org)
  • deposits
  • Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. (docme.ru)
  • For a period, the scientific community debated whether or not amyloid deposits are fatty deposits or carbohydrate deposits until it was finally found (in 1859) that they are, in fact, deposits of albumoid proteinaceous material. (wikipedia.org)
  • These deposits often recruit various sugars and other components such as Serum Amyloid P component, resulting in complex, and sometimes inhomogeneous structures. (wikipedia.org)
  • type
  • Restoration of wild-type p53 function has been shown to effectively suppress tumor growth in mice, but has proven difficult to achieve in patients. (aacrjournals.org)
  • functional
  • In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. (docme.ru)
  • Notably, the present review will focus on the detailed functional roles of amyloid in immune response characterized as autoimmunity and anti-inflammatory response. (docme.ru)
  • homeostasis
  • Hence, we summarize the current knowledge and advanced understanding regarding the determinant role of amyloid in immune homeostasis, as well as maladaptive inflammatory response leading to amyloid disease and other amyloid-relevant disease. (docme.ru)
  • To gain insight into the role of Asna1/TRC40 in maintaining endomembrane homeostasis and β-cell function, we inactivated Asna1 in β-cells of mice. (diabetesjournals.org)
  • human
  • 2016). However, improved outcomes have become to compromise the emerging regressive effect caused by immunotherapeutic targeting, implying amyloid is a multifaceted player in human health and disease (Johansson et al. (docme.ru)
  • membrane
  • Innate immune cells, such as macrophages, can induce inflammatory responses through detection of a variety of pathogen- or damage-associated molecular patterns using innate sensors, i.e., membrane-bound TLRs or cytosolic Nod-like receptors (NLRs) ( 6 ). (diabetesjournals.org)
  • Loss of Asna1 function leads to perturbed plasma membrane-to- trans Golgi network and Golgi-to-ER retrograde transport as well as to ER stress in β-cells. (diabetesjournals.org)
  • cell
  • The primary function of a beta cell is to store and release insulin. (wikipedia.org)
  • Recent advances in understanding the mechanism(s) of how IL-6 trans -signaling regulates immune cell function and promotes inflammation in autoimmune arthritis are critically reviewed. (dovepress.com)
  • biological activity
  • The recognition that IL-6 trans -signaling regulates inflammation resulted in the development of tocilizumab, a fully humanized monoclonal antibody that neutralizes the biological activity of the IL-6-receptor (IL-6R). (dovepress.com)
  • specific
  • It is believed to be due to the decline of specific receptors on the surface of the liver and muscle cells which lose their ability to respond to insulin that circulates in the blood. (wikipedia.org)