Heparin oligosaccharides that pass the blood-brain barrier inhibit β-amyloid precursor protein secretion and heparin binding to β-amyloid peptide

Béatrice Leveugle Wanhong Ding Laurence Fenart 1 Marie-Pierre Dehouck 1 Andrew Scanameo Roméo Cecchelli 1 Howard Fillit
1 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique
Abstract : We have previously demonstrated that full-length heparin stimulates the synthesis and secretion of β-amyloidprecursor protein (APP) through an amyloidogenic pathway in neuroblastoma cells. In the present study, heparin was chemically depolymerized, and the effect of low-molecular-weight (LMW) hepanin on APP secretion was investigated. In contrast to full-length hepar, LMW heparin had no significant effect on APP secretion. However, LMW heparin fragments, especially heparin disaccharides, were able to inhibit efficiently the stimulatory effect of heparin on APP secretion. LMW heparin derivatives also inhibit the binding of heparin to the β-amyloid peptide (1-28). Using an in vitro model, we further demonstrated the passage of LMW heparin derivatives through the blood-brain barrier. This study suggests that LMW heparin derivatives or analogues may be effective as therapeutic agents to prevent or slow the process of amyloidogenesis in Alzheimer's disease.
Keywords : Heparan sulfate Alzheimer's disease Proteoglycans Glycosaminoglycans Therapy
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Journal articles
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Contributor : Wilfried Déplanques <>
Submitted on : Friday, October 8, 2010 - 4:01:28 PM
Last modification on : Friday, October 8, 2010 - 4:01:28 PM

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Béatrice Leveugle, Wanhong Ding, Laurence Fenart, Marie-Pierre Dehouck, Andrew Scanameo, et al.. Heparin oligosaccharides that pass the blood-brain barrier inhibit β-amyloid precursor protein secretion and heparin binding to β-amyloid peptide. Journal of Neurochemistry, Wiley, 1998, 70 (2), p. 736-744. ⟨hal-00524713⟩

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