Publications by authors named "Pierre-Alexandre Driguez"

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.

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Heparan 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.

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NMR 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.

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Article Synopsis
  • The molecular interactions between gut bacteria and humans, particularly with the bacterium Bacteroides thetaiotaomicron, are not well understood despite their physiological relevance.
  • Recent research highlights the role of sulfatases in helping this bacterium adapt to and flourish in the human gut by metabolizing complex sugars known as glycosaminoglycans (GAGs).
  • This study identifies and characterizes four specific GAG sulfatases for the first time, revealing that B. thetaiotaomicron possesses a unique endosulfatase that operates on these complex sugars at a polymer level, indicating a more intricate bacterial capability in processing host glycans than previously thought.
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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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Article Synopsis
  • FGF signaling plays a crucial role in mammalian development and metabolism, and its disruption is linked to various diseases, particularly cancer.
  • Heparan sulfate glycosaminoglycans (HSGAGs) are vital for FGF signaling as they enhance the binding and dimerization of FGF with its receptor FGFR.
  • In experiments, homogeneously sulfated heparin mimetics (HM) were created, showing that larger HM (like HM(8) and HM(10)) are more effective than smaller versions (HM(6)) at enhancing FGF2-FGFR4 signaling, correlating with their binding efficiency and promoting a refined model of FGF dimerization.
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