title: Anti-HSV1 activity of brown algal polysaccharides and possible relevance to the treatment of Alzheimer's disease.
abstract: Herpes simplex virus type 1 (HSV1) induces the formation of the characteristic abnormal molecules of Alzheimer's disease (AD) brains, beta-amyloid, and abnormally phosphorylated, AD-like tau (P-tau). Formation of these molecules is inhibited by treatment with the antiviral agent acyclovir (ACV), which prevents viral DNA replication. A totally different mechanism of antiviral action against herpes simplex viruses is shown by sulfated fucans. The antiviral activity of sulfated fucans from five brown algae (Scytothamnus australis, Marginariella boryana, Papenfussiella lutea, Splachnidium rugosum and Undaria pinnatifida) was investigated in relation to the HSV1-induced formation of beta-amyloid, and AD-like tau. Antiviral activity was also related to specific structural features of these polysaccharides. Four sulfated fucan extracts each prevented the accumulation of HSV1-induced beta-amyloid and AD-like tau in HSV1-infected Vero cells. The structures of these extracts had some similarities but also key differences, indicating that a number of structural features can cause antiviral activity. The most active sulfated fucan combined with acyclovir was particularly effective, so may be particularly suitable for further experimental testing in order to develop treatment protocols for AD patients, with the aim of slowing or stopping disease progression.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, 3.545 Stopford Building, Oxford Road, Manchester M13 9PT, UK. Electronic address: matthew.wozniak@tinyonline.co.uk.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wozniak
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington, PO Box 31-310, Lower Hutt, New Zealand. Electronic address: Tracey.Bell@vuw.ac.nz.
authors.forename: Tracey
authors.initials: T
authors.lastname: Bell
authors.affiliation: Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u 43, Budapest H 1083, Hungary. Electronic address: denes.adam@koki.mta.hu.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Dénes
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington, PO Box 31-310, Lower Hutt, New Zealand. Electronic address: r.falshaw@xtra.co.nz.
authors.forename: Ruth
authors.initials: R
authors.lastname: Falshaw
authors.affiliation: Faculty of Life Sciences, The University of Manchester, 3.545 Stopford Building, Oxford Road, Manchester M13 9PT, UK. Electronic address: ruth.itzhaki@manchester.ac.uk.
authors.forename: Ruth
authors.initials: R
authors.lastname: Itzhaki
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D000459:Phaeophyceae / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells; D016875:tau Proteins
chemical_list: D016229:Amyloid beta-Peptides; D000998:Antiviral Agents; D011134:Polysaccharides; D016875:tau Proteins; C007789:fucoidan
keywords: Alzheimer's disease; Antiviral; Fucan