• degradation
  • Contrary, inhibition of cathepsin S will lead to a delay in degradation of Ii and loading the antigen into MHC II as well as inappropriate presence of uncleaved Li-fragments in MHC II on the cell surface. (wikipedia.org)
  • Based upon the aforementioned observation in protein structure, it has been proposed that a possible therapeutic approach to Alzheimer's might involve shifting the conformational preference of IDE to the open state, and thus increasing Aβ degradation, preventing aggregation, and, ideally, preventing the neuronal loss that leads to disease symptoms. (wikipedia.org)
  • molecules
  • In particular, exosomal molecules, including proteins, lipids, and nucleic acids, have been suggested as disease biomarkers or therapeutic targets in various diseases. (einj.org)
  • lipids
  • Among these, the secretion and uptake of molecular contents, including proteins, lipids, metabolites, and nucleic acids, from adjacent or remote cells is an efficient system that modulates cellular homeostasis and adaptation. (einj.org)
  • There is extensive evidence that cholesterol and membrane lipids play a key role in Alzheimer disease (AD) pathogenesis. (rupress.org)
  • neuroinflammation
  • Acute neuroinflammation is generally caused by some neuronal injury after which microglia migrate to the injured site engulfing dead cells and debris. (wikipedia.org)
  • In chronic neuroinflammation, microglia remain activated for an extended period during which the production of mediators is sustained longer than usual. (wikipedia.org)
  • Hippocampus
  • Mounting data suggests that another factor, the tau protein ripens into highly phosphorylated form by several kinases after Aβ-stimulation leads to tangle formation resulting in neuronal bereavement in hippocampus and entorhinal regions as the disease progresses further. (ijpsonline.com)
  • brain
  • Matsumoto et al, "Human brain beta-secretase contains heparan sulfate glycoconjugates," Neurosci. (patentgenius.com)
  • Composition of white matter bovine brain coated vesicles: evidence that several components influence .beta. (patentgenius.com)
  • Microglia constitute 10-15% of all cells found within the brain. (omicsgroup.org)
  • Due to the unavailability of antibodies from the rest of the body (few antibodies are small enough to cross the blood-brain barrier), microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells . (omicsgroup.org)
  • During hematopoiesis , some of these stem cells differentiate into monocytes and travel from the bone marrow to the brain, where they settle and further differentiate into microglia. (omicsgroup.org)
  • However, recent studies indicate microglia originate in the yolk sac during a remarkably restricted period and populate the brain mesenchyme. (omicsgroup.org)
  • Due to the blood-brain barrier , it would be fairly difficult for the body to constantly replace microglia. (omicsgroup.org)
  • induce
  • OLE is able to induce autophagy, achieving a decrease of aggregated proteins and a reduction of cognitive impairment in vivo. (hindawi.com)
  • lysosomal
  • Autophagy is a physiological process by which aggregated proteins and damaged organelles are eliminated through lysosomal digestion. (hindawi.com)
  • mediators
  • These mediators are important in the normal functions of microglia and their production is usually decreased once their task is complete. (wikipedia.org)
  • alpha-synuclein
  • 7. The method of claim 2 wherein the synuclein is alpha synuclein or beta synuclein. (google.ca)
  • printed instructions for reacting the agent with the biological sample for detecting an amount of one or more of neurensin (p24), UCH-L1, alpha-synuclein and beta-synuclein. (google.ca)
  • Other proteins such as superoxide dismutase I and alpha-synuclein (involved in amyotrophic lateral sclerosis and Parkinson's disease, respectively) are also found associated with exosomes. (frontiersin.org)
  • mechanisms
  • Identifying these unknown de novo mRNA targets from cellular extracts in the RNP complex is pivotal to understanding mechanisms and functions of the RBP and their resulting effect on protein output. (jove.com)
  • Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. (frontiersin.org)
  • Cholesterol homeostasis is tightly regulated by feedback mechanisms: sterol regulatory element binding proteins (SREBPs) and liver X receptors (LXRs) regulate the expression of genes that control the uptake, synthesis, and export of cholesterol. (rupress.org)
  • cells
  • Microglial cells are sources of some chemokines and express the monocyte chemoattractant protein-1 (MCP-1) chemokine in particular. (wikipedia.org)
  • Proposed functions of these vesicles include roles in cell-cell signaling, removal of unwanted proteins, and the transfer of pathogens between cells. (frontiersin.org)
  • Roles for these vesicles include cell-cell signaling, removal of unwanted proteins, and transfer of pathogens, such as prions, between cells. (frontiersin.org)
  • Several studies have detected insulin-degrading activity in the conditioned media of cultured cells, suggesting the permeability of the cell membrane and thus possible release of IDE from leaky cells. (wikipedia.org)
  • Another difference between microglia and other cells that differentiate from myeloid progenitor cells is the turnover rate. (omicsgroup.org)
  • Therefore, instead of constantly being replaced with myeloid progenitor cells , the microglia maintain their status quo while in their quiescent state, and then, when they are activated, they rapidly proliferate in order to keep their numbers up. (omicsgroup.org)
  • immune
  • The constitutive production of large amounts of IL-1α precursor by healthy epidermal keratinocytes interfere with the important role of IL-1α in immune responses, assuming skin as a barrier, which prevents the entry of pathogenic microorganisms into the body. (wikipedia.org)
  • potentially
  • Since this process must be done quickly to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS. (omicsgroup.org)
  • isolation
  • However, several unresolved issues and challenges remain despite these promising results, including source variability before the isolation of exosomes from body fluids, the contamination of proteins during isolation, and methodological issues related to the purification of exosomes. (einj.org)
  • Complex
  • Cathepsin S cleaves the remaining fragment of Ii (IiP1) and leaves a small part of Ii known as CLIP which stays directly associated with the complex. (wikipedia.org)
  • Driven by the binding of RNA Binding Proteins (RBP), post-transcriptional regulation affects mRNA localization, stability and translation by forming a Ribonucleoprotein (RNP) complex with target mRNAs. (jove.com)
  • receptors
  • The nociceptive activity results from cathepsin S functioning as a signaling molecule via activation of protease-activated receptors 2 and 4 members of the G-protein coupled receptor family. (wikipedia.org)
  • consist
  • It was not until 1985 that interleukin 1 was discovered to consist of two distinct proteins, now called interleukin-1 alpha and interleukin-1 beta. (wikipedia.org)
  • genes
  • this can happen when there is a mutation in one of the genes that creates a functional, but malformed, protein instead of the ineffective gene products that usually result from mutations. (wikipedia.org)
  • disease
  • The cellular prion protein (PrP C ) is known for its crucial involvement, via its scrapie isoform PrP Sc , in the development of transmissible spongiform encephalopathies (TSEs), such as Creutzfeldt-Jakob disease in man and scrapie in sheep and goats. (frontiersin.org)
  • In many research and disease models however, steady state levels of target gene mRNA does not always directly correlate with steady state protein levels. (jove.com)