Novel heparan sulphate analogues: inhibition of beta-secretase cleavage of amyloid precursor protein.
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.
Patey
S J
SJ
Molecular Glycobiology Research Group, School of Biological Sciences, The University of Liverpool, Liverpool L69 7ZB, UK. s.j.patey@liv.ac.uk
Yates
E A
EA
Turnbull
J E
JE
D000544:Alzheimer Disease / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases; D010450:Endopeptidases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans
D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor; D016282:Aspartic Acid Endopeptidases; D010450:Endopeptidases; D004791:Enzyme Inhibitors; D006497:Heparan Sulfate; C509280:BACE1 protein, human