A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer's Disease.

Mycroft-West, CJ; Cooper, LC; Devlin, AJ; Procter, P; Guimond, SE; Guerrini, M; Fernig, DG; Lima, MA; Yates, EA; Skidmore, MA

doi:10.3390/md17050293

A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer's Disease.

Mycroft-West, CJ; Cooper, LC; Devlin, AJ; Procter, P; Guimond, SE; Guerrini, M; Fernig, DG; Lima, MA; Yates, EA; Skidmore, MA

Authors

CJ Mycroft-West

LC Cooper

AJ Devlin

Patricia Procter p.procter@keele.ac.uk

Scott Guimond s.e.guimond@keele.ac.uk

M Guerrini

DG Fernig

Marcelo Andrade De Lima m.andrade.de.lima@keele.ac.uk

EA Yates

Mark Skidmore m.a.skidmore@keele.ac.uk

Abstract

Therapeutic options for Alzheimer's disease, the most common form of dementia, are currently restricted to palliative treatments. The glycosaminoglycan heparin, widely used as a clinical anticoagulant, has previously been shown to inhibit the Alzheimer's disease-relevant β-secretase 1 (BACE1). Despite this, the deployment of pharmaceutical heparin for the treatment of Alzheimer's disease is largely precluded by its potent anticoagulant activity. Furthermore, ongoing concerns regarding the use of mammalian-sourced heparins, primarily due to prion diseases and religious beliefs hinder the deployment of alternative heparin-based therapeutics. A marine-derived, heparan sulphate-containing glycosaminoglycan extract, isolated from the crab Portunus pelagicus, was identified to inhibit human BACE1 with comparable bioactivity to that of mammalian heparin (IC50 = 1.85 μg mL-1 (R2 = 0.94) and 2.43 μg mL-1 (R2 = 0.93), respectively), while possessing highly attenuated anticoagulant activities. The results from several structural techniques suggest that the interactions between BACE1 and the extract from P. pelagicus are complex and distinct from those of heparin.

Journal Article Type	Article
Acceptance Date	May 9, 2019
Publication Date	May 16, 2019
Publicly Available Date	May 26, 2023
Journal	Marine Drugs
Electronic ISSN	1660-3397
Publisher	MDPI
Volume	17
Pages	293 -293
DOI	https://doi.org/10.3390/md17050293
Keywords	Alzheimer’s disease, BACE1, Portunus pelagicus, amyloid-β, glycosaminoglycan, heparan sulphate, heparin, β-secretase, Alzheimer Disease, Amyloid Precursor Protein Secretases, Animals, Anticoagulants, Aspartic Acid Endopeptidases, Brachyura, Enzyme Act
Publisher URL	https://www.ncbi.nlm.nih.gov/pubmed/31100859