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A sulphated glycosaminoglycan extract from Placopecten magellanicus inhibits the Alzheimer's disease ß-site amyloid precursor protein cleaving enzyme 1 (BACE-1).

Mycroft-West, CJ; Devlin, AJ; Cooper, LC; Guimond, S; Procter, P; Miller, G; Guerrini, M; Fernig, DG; Yates, EA; Andrade De Lima, M; Skidmore, M


CJ Mycroft-West

AJ Devlin

LC Cooper

P Procter

M Guerrini

DG Fernig

EA Yates

M Skidmore


The clinically important anticoagulant heparin, a member of the glycosaminoglycan family of carbohydrates that is extracted predominantly from porcine and bovine tissue sources, has previously been shown to inhibit the ß-site amyloid precursor protein cleaving enzyme 1 (BACE-1), a key drug target in Alzheimer's Disease. In addition, heparin has been shown to exert favourable bioactivities through a number of pathophysiological pathways involved in the disease processes of Alzheimer's Disease including inflammation, oxidative stress, tau phosphorylation and amyloid peptide generation. Despite the multi-target potential of heparin as a therapeutic option for Alzheimer's disease, the repurposing of this medically important biomolecule has to-date been precluded by its high anticoagulant potential. An alternative source to mammalian-derived glycosaminoglycans are those extracted from marine environments and these have been shown to display an expanded repertoire of sequence-space and heterogeneity compared to their mammalian counterparts. Furthermore, many marine-derived glycosaminoglycans appear to retain favourable bioactivities, whilst lacking the high anticoagulant potential of their mammalian counterparts. Here we describe a sulphated, marine-derived glycosaminoglycan extract from the Atlantic Sea Scallop, Placopecten magellanicus that displays high inhibitory potential against BACE-1 (IC50 = 4.8 µg.mL-1) combined with low anticoagulant activity; 25-fold less than that of heparin. This extract possesses a more favourable therapeutic profile compared to pharmaceutical heparin of mammalian provenance and is composed of a mixture of heparan sulphate (HS), with a high content of 6-sulphated N-acetyl glucosamine (64%), and chondroitin sulphate.

Journal Article Type Article
Acceptance Date Jan 19, 2023
Online Publication Date Jan 26, 2023
Publication Date Mar 1, 2023
Publicly Available Date Jan 27, 2024
Journal Carbohydrate Research
Print ISSN 0008-6215
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 525
Article Number 108747
Keywords Alzheimer?s disease; Amyloid-0; BACE-1; 0-secretase; 0-site amyloid precursor protein cleaving; enzyme 1; Glycosaminoglycan; Chondroitin sulphate; Heparin; Heparan sulphate; Placopecten magellanicus
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