A glycosaminoglycan extract from Portunus pelagicus inhibits BACE1, the β secretase implicated in Alzheimer’s disease

Mycroft-West, Courtney J., Cooper, Lynsay C ORCID: 0000-0002-5100-5261, Devlin, Anthony J., Procter, Patricia, Guimond, Scott E., Guerrini, Marco, Fernig, David G., Lima, Marcelo A., Yates, Edwin A. and Skidmore, Mark A. (2019) A glycosaminoglycan extract from Portunus pelagicus inhibits BACE1, the β secretase implicated in Alzheimer’s disease. Marine Drugs, 17 (5). p. 293. doi:10.3390/md17050293

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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.

Item Type: Article
Article Type: Article
Uncontrolled Keywords: Alzheimer’s disease; Amyloid-β; BACE1; β-secretase; Glycosaminoglycan; Heparan sulphate; Heparin; Portunus pelagicus
Subjects: Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Schools and Research Institutes > School of Natural & Social Sciences > Environmental Sciences
Research Priority Areas: Place, Environment and Community
Depositing User: Lynsay Cooper
Date Deposited: 24 Aug 2021 15:39
Last Modified: 25 Aug 2021 09:30
URI: http://eprints.glos.ac.uk/id/eprint/10070

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