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

Autor: Mycroft-West CJ; Centre for Glycoscience Research and Training, Keele University, Keele, Staffordshire, ST5 5BG, UK. Electronic address: courtney.mycroft-west@rfi.ac.uk., Devlin AJ; Centre for Glycoscience Research and Training, Keele University, Keele, Staffordshire, ST5 5BG, UK; Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Via G. Colombo 81, 20133, Milan, Italy. Electronic address: anthony.devlin@rfi.ac.uk., Cooper LC; University of Gloucestershire, Francis Close Hall Campus, Swindon Rd, Cheltenham, GL50 4AZ, UK. Electronic address: lcooper1@glos.ac.uk., Guimond SE; Centre for Glycoscience Research and Training, Keele University, Keele, Staffordshire, ST5 5BG, UK. Electronic address: s.e.guimond@keele.ac.uk., Procter P; Centre for Glycoscience Research and Training, Keele University, Keele, Staffordshire, ST5 5BG, UK. Electronic address: p.procter@keele.ac.uk., Miller GJ; Centre for Glycoscience Research and Training, Keele University, Keele, Staffordshire, ST5 5BG, UK. Electronic address: g.j.miller@keele.ac.uk., Guerrini M; Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Via G. Colombo 81, 20133, Milan, Italy. Electronic address: guerrini@ronzoni.it., Fernig DG; Department of Biochemistry and Systems Biology, ISMIB, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK. Electronic address: dgfernig@liverpool.ac.uk., Yates EA; Department of Biochemistry and Systems Biology, ISMIB, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK. Electronic address: E.A.Yates@liverpool.ac.uk., Lima MA; Centre for Glycoscience Research and Training, Keele University, Keele, Staffordshire, ST5 5BG, UK. Electronic address: m.andrade.de.lima@keele.ac.uk., Skidmore MA; Centre for Glycoscience Research and Training, Keele University, Keele, Staffordshire, ST5 5BG, UK; Department of Biochemistry and Systems Biology, ISMIB, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK. Electronic address: m.a.skidmore@keele.ac.uk.
Jazyk: angličtina
Zdroj: Carbohydrate research [Carbohydr Res] 2023 Mar; Vol. 525, pp. 108747. Date of Electronic Publication: 2023 Jan 26.
DOI: 10.1016/j.carres.2023.108747
Abstrakt: 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 β-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 (IC 50  = 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.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mark Skidmore reports financial support was provided by IntelliHep Ltd. Mark Skidmore reports financial support was provided by MI Engineering Limited. Courtney Mycroft-West reports financial support was provided by IntelliHep Ltd. Anthony Devlin reports financial support was provided by MI Engineering Limited. Edwin Yates reports a relationship with IntelliHep Ltd that includes: board membership and equity or stocks.
(Copyright © 2023. Published by Elsevier Ltd.)
Databáze: MEDLINE
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