Binding of heparan sulfate glycosaminoglycan to beta-amyloid peptide: inhibition by potentially therapeutic polysulfated compounds.
Heparin sulfate proteoglycans are believed to play an important role in amyloidosis as pathologic chaperones. They bind to amyloidogenic proteins and may mediate the deposition and fibrillogenesis of amyloid at specific tissue sites. In the present study, we demonstrate that heparin sulfate glycosaminoglycan and proteoglycan both bind to the beta-amyloid peptide involved in Alzheimer's disease. The interaction of heparan sulfate proteoglycan and glycosaminoglycan can be inhibited by other sulfated compounds such as heparin, dextran sulfate and pentosan polysulfate. These polysaccharides which are currently used clinically, their derivatives or analogs may be effective as therapeutic agents to prevent or slow the progression of amyloidogenesis in Alzheimer's disease or other amyloidogenic disorders.
Leveugle
B
B
Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New York, NY 10029-6574.
Scanameo
A
A
Ding
W
W
Fillit
H
H
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001667:Binding, Competitive; D002846:Chromatography, Affinity; D016264:Dextran Sulfate / Q000494:pharmacology; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000302:isolation & purification / Q000378:metabolism*; D009447:Neuroblastoma / Q000737:chemistry; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011509:Proteoglycans / Q000302:isolation & purification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D016264:Dextran Sulfate; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D010426:Pentosan Sulfuric Polyester; D011134:Polysaccharides; D011509:Proteoglycans; D013431:Sulfates