Novel heparan sulphate analogues: inhibition of beta-secretase cleavage of amyloid precursor protein

Biochem Soc Trans. 2005 Nov;33(Pt 5):1116-8. doi: 10.1042/BST20051116.

Abstract

The role of HS (heparan sulphate) in the pathology of AD (Alzheimer's disease) is multifaceted. HS and other glycosaminoglycans have been widely reported to be associated with neuritic plaques. HS has also been shown to promote the aggregation of Abeta (amyloid beta-peptide), the proteinaceous component of neuritic plaques. Recently, we described a novel and contrasting role for HS in the pathology of AD: HS can inhibit the formation of Abeta, by directly interacting with the protease BACE1 (beta-site amyloid precursor protein cleaving enzyme 1; beta-secretase 1), that cleaves the amyloid precursor protein and is the rate limiting step in the generation of Abeta. Here, we review the current roles of HS and the potential for HS-derivatives in the treatment of AD.

MeSH terms

  • Alzheimer Disease / physiopathology
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor / metabolism*
  • Aspartic Acid Endopeptidases
  • Endopeptidases / metabolism*
  • Enzyme Inhibitors / pharmacology*
  • Heparitin Sulfate / analogs & derivatives*
  • Heparitin Sulfate / pharmacology*
  • Humans

Substances

  • Amyloid beta-Protein Precursor
  • Enzyme Inhibitors
  • Heparitin Sulfate
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human