The receptor Triggering Receptor Expressed on Myeloid cells 2 (TREM2) is associated with several neurodegenerative diseases including Alzheimer's Disease and TREM2 stimulation represents a novel therapeutic opportunity. TREM2 can be activated by antibodies targeting the stalk region, most likely through receptor dimerization. Endogenous ligands of TREM2 are suggested to be negatively charged apoptotic bodies, mimicked by phosphatidylserine incorporated in liposomes and other polyanionic molecules likely binding to TREM2 IgV fold.
View Article and Find Full Text PDFHeparan sulfates are complex polysaccharides belonging to the family of glycosaminoglycans that participate to the regulation of cell behavior and tissue homeostasis. The biological activities conferred to heparan sulfates are largely dependent on the content and positioning of the sulfate groups along their saccharidic units. At present, identification of particular sulfation patterns in biologically relevant heparan sulfate sequences remains challenging.
View Article and Find Full Text PDFNMR and density functional theory (DFT) have afforded detailed information on the molecular geometry and spin-spin coupling constants of a trisaccharide from the heparin repeating-sequence. The fully optimized molecular structures of two trisaccharide conformations (differing from each other in the form of the central iduronic acid residue) were obtained using the B3LYP/6-311+G(d,p) level of theory in the presence of solvent, the latter included as either explicit water molecules or via a continuum solvent model. NMR spin-spin coupling constants were also computed using various basis sets and functionals and then compared with measured experimental values.
View Article and Find Full Text PDFJ Biol Chem
August 2014
Covering: up to November 2013. Heparin and heparan sulfate are natural polysaccharides with strong structural variations, which are responsible for their numerous specific biological properties. One key target of heparin, among others, is antithrombin, a serine protease inhibitor that, upon activation, mainly targets anticoagulation factors IIa and Xa.
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