title: An extract of the marine alga Alaria esculenta modulates α-synuclein folding and amyloid formation.
abstract: The conversion of α-synuclein from its natively unfolded and α-helical tetrameric forms to an amyloid conformation is central to the emergence of Parkinson's disease. Therefore, prevention of this conversion may offer an effective way of avoiding the onset of this disease or delaying its progress. At different concentrations, an aqueous extract from the edible winged kelp (Alaria esculenta), was shown to lower and to raise the melting point of α-synuclein. Size fractionation of the extract resulted in the separation of these distinct activities. The fraction below 5kDa decreased the melting point of α-synuclein, whereas the fraction above 10kDa raised the melting point. Both of these fractions were found to inhibit the formation of amyloid aggregates by α-synuclein, measured by thioflavin T dye-binding assays; this effect was further confirmed by transmission electron microscopy showing the inhibition of fibril formation. Circular dichroism analysis suggested that the incubation of α-synuclein under fibrillation conditions resulted in the loss of substantial native helical structure in the presence and absence of the fractions. It is therefore likely that the fractions inhibit fibrillation by interacting with the unfolded form of α-synuclein.
authors.affiliation: Department of Biology, Dalhousie University, P.O. Box 15000, Halifax, NS B3H 4R2, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Giffin
authors.affiliation: Aquatic and Crop Resource Development, National Research Council,Sandy Cove Road, Ketch Harbour, NS B3 V 1K9, Canada.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Richards
authors.affiliation: Aquatic and Crop Resource Development, National Research Council,1411 Oxford St., Halifax, NS B3H 3Z1, Canada.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Craft
authors.affiliation: Aquatic and Crop Resource Development, National Research Council,1411 Oxford St., Halifax, NS B3H 3Z1, Canada.
authors.forename: Nusrat
authors.initials: N
authors.lastname: Jahan
authors.affiliation: Aquatic and Crop Resource Development, National Research Council,Sandy Cove Road, Ketch Harbour, NS B3 V 1K9, Canada.
authors.forename: Cindy
authors.initials: C
authors.lastname: Leggiadro
authors.affiliation: Canadian Integrated Multi-Trophic Aquaculture Network, University of New Brunswick, Saint John, NB E2L 4L5, Canada.
authors.forename: Thierry
authors.initials: T
authors.lastname: Chopin
authors.affiliation: Cooke Aquaculture Inc., 874 Main St, Blacks Harbour, NB E5H 1E6, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Szemerda
authors.affiliation: Aquatic and Crop Resource Development, National Research Council,1411 Oxford St., Halifax, NS B3H 3Z1, Canada.
authors.forename: Shawna L
authors.initials: SL
authors.lastname: MacKinnon
authors.affiliation: Department of Biology, Dalhousie University, P.O. Box 15000, Halifax, NS B3H 4R2, Canada; Department of Biochemistry and Molecular Biology, Dalhousie University, P.O. Box 15000, Halifax, NS B3H 4R2, Canada. Electronic address: vewart@dal.ca.
authors.forename: K Vanya
authors.initials: KV
authors.lastname: Ewart
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D017510:Protein Folding / Q000187:drug effects*; D012624:Seaweed; D051844:alpha-Synuclein / Q000737:chemistry / Q000187:drug effects*
chemical_list: D000682:Amyloid; D010936:Plant Extracts; D051844:alpha-Synuclein
keywords: Alaria esculenta; Alpha-synuclein; Amyloid; Brown seaweed; Parkinson’s disease; Protein misfolding