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

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.

Citation

Mycroft-West, C., Cooper, L., Devlin, A., Procter, P., Guimond, S., Guerrini, M., …Skidmore, M. (2019). A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer's Disease. Marine Drugs, 17, 293 -293. https://doi.org/10.3390/md17050293

• 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