Mycroft-West, Courtney J, Cooper, Lynsay C, Devlin, Anthony J, Procter, Patricia, Guimond, Scott E, Guerrini, Marco, Fernig, David G 
ORCID: 0000-0003-4875-4293, Lima, Marcelo A, Yates, Edwin A ORCID: 0000-0001-9365-5433 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).
E293-.
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A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer's Disease.pdf - Published version Download (3MB) | Preview |
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 <i>Portunus pelagicus</i>, was identified to inhibit human BACE1 with comparable bioactivity to that of mammalian heparin (IC<sub>50</sub> = 1.85 μg mL<sup>-1</sup> (R<sup>2</sup> = 0.94) and 2.43 μg mL<sup>-1</sup> (R<sup>2</sup> = 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 <i>P. pelagicus</i> are complex and distinct from those of heparin.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Alzheimer's disease, amyloid- beta, BACE1, beta-secretase, glycosaminoglycan, heparan sulphate, heparin, Portunus pelagicus |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 08 Jul 2019 14:09 |
| Last Modified: | 07 Feb 2024 23:35 |
| DOI: | 10.3390/md17050293 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3049150 |
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