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Dysregulation of amyloidogenic proteins and their abnormal processing and deposition in tissues cause systemic and localized amyloidosis. Formation of amyloid β (Aβ) fibrils that deposit as amyloid plaques in Alzheimer's disease (AD) brains is an earliest pathological hallmark. The polysulfated heparan sulfate (HS)/heparin (HP) is one of the non-protein components of Aβ deposits that not only modulates Aβ aggregation, but also acts as a receptor for Aβ fibrils to mediate their cytotoxicity. Interfering with the interaction between HS/HP and Aβ could be a therapeutic strategy to arrest amyloidosis. Here we have synthesized the 6-O-phosphorylated HS/HP oligosaccharides and reported their competitive effects on the inhibition of HP-mediated Aβ fibril formation in vitro using a thioflavin T fluorescence assay and a tapping mode atomic force microscopy.
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http://dx.doi.org/10.1002/cbic.202200191 | DOI Listing |
J Clin Invest
September 2025
Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America.
3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of Antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding HS (HSAT) is expressed in human tissues, but is thought to be expressed in the subendothelial space, mast cells, and follicular fluid.
View Article and Find Full Text PDFNephrol Dial Transplant
September 2025
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Background: We investigated circulating protein profiles and molecular pathways among various chronic kidney disease (CKD) etiologies to study its underlying molecular heterogeneity.
Methods: We conducted a proteomic biomarker analysis in the DAPA-CKD trial recruiting adults with and without type 2 diabetes with an eGFR of 25 to 75 mL/min/1.73m2 and a UACR of 200 to 5000 mg/g.
Dev Biol
September 2025
Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115 USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115 USA; Harvard Stem Cell Institute, 7 Divinity Ave, Cambridge, MA 02138 USA. Electronic address:
The mechanisms mediating endochondral bone formation remain incompletely understood. Here, we show that CXXC Finger Protein 1 (CFP1) is required for the onset of chondrogenesis during forelimb development. CFP1-deficient mesenchymal progenitor cells (LMPs) retain an immature molecular signature with elevated FGF and SHH signaling and repressed BMP signaling, in part, due to (1) reduced expression of type I BMP receptors, (2) reduced Smad1 protein levels and (3) an altered extracellular niche.
View Article and Find Full Text PDFCarbohydr Polym
November 2025
Departments of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.. Electronic address:
A naturally derived library of glycomimetic mimicking the structure-function of heparan sulfate (HS) remains an untapped reservoir for drug discovery against viral infections. In this work we screened a library of marine-derived sulfated glycans from seaweeds and sea cucumbers to investigate if they can compete for the ligand/receptor binding sites to prevent virus entry. Multiple promising candidates were identified, such as RPI-27 (IC: 1.
View Article and Find Full Text PDFSci Adv
September 2025
School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
The transition from unicellular to multicellular life required the acquisition of coordinated and regulated cellular behaviors, including adhesion and migration. In metazoans, this involves adhesion proteins, signaling systems, and an elaborate extracellular matrix (ECM) that contributes to adhesion and signaling interactions. Innovations that enabled complex multicellularity occurred through new genes in these pathways, novel functions for existing genes, and regulatory changes.
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