title: Modulation effect of filamentous phage on alpha-synuclein aggregation.
abstract: Conversion of soluble peptides and proteins into amyloid fibrils and/or intermediate oligomers is believed to be the central event in the pathogenesis of most human neurodegenerative diseases, including Parkinson's disease (PD). Here we describe the modulating effect of filamentous phages on aggregation of alpha-synuclein (AS) in vitro and in a PD cellular model. Filamentous phages, well understood at both structural and genetic levels, have a nanotubular appearance, showing conformational similarities to amyloid fibrils. Since filamentous phages can infect only bacteria and have no tropism to mammalian cells, we utilized the f88 system to present a peptide containing a cyclic RGD (arg-gly-asp), which enabled phage internalization into the cells. Detection of intracellular AS oligomers, in differentiated SH-SY5Y cells, stably transfected with wild type AS gene, was performed using Western blot and ELISA measurements. Data presented here show reduced levels of AS soluble aggregates in phage treated cells compared to non-treated cells, suggesting new therapeutics for PD.
authors.affiliation: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel.
authors.forename: Hemi
authors.initials: H
authors.lastname: Dimant
authors.forename: Noa
authors.initials: N
authors.lastname: Sharon
authors.forename: Beka
authors.initials: B
authors.lastname: Solomon
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D017912:Inovirus / Q000378:metabolism*; D008954:Models, Biological; D049329:Nanostructures / Q000627:therapeutic use*; D009842:Oligopeptides / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism / Q000628:therapy*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D009842:Oligopeptides; D051844:alpha-Synuclein; C047981:arginyl-glycyl-aspartic acid