title: Vitamin D 2 interacts with Human PrP(c) (90-231) and breaks PrP(c) oligomerization in vitro.
abstract: PrP(sc), the pathogenic isoform of PrP(c), can convert PrP(c) into PrP(sc) through direct interactions. PrP(c) oligomerization is a required processing step before PrP(sc) formation, and soluble oligomers appear to be the toxic species in amyloid-related disorders. In the current study, direct interactions between vitamin D 2 and human recombinant PrP(c) (90-231) were observed by Biacore assay, and 3F4 antibody, specific for amino acid fragment 109-112 of PrP(c), inhibited this interaction. An ELISA study using3F4 antibody showed that PrP(c) (101-130), corresponding sequence to human PrP, was affected by vitamin D 2, supporting the results of Biacore studies and suggesting that the PrP(c) sequence around the 3F4 epitope was responsible for the interaction with vitamin D 2. Furthermore, the effects of vitamin D 2 on disruption of PrP(c) (90-231) oligomerization were elucidated by dot blot analysis and differential protease k susceptibilities. While many chemical compounds have been proposed as potential therapeutic agents for the treatment of scrapie, most of these are toxic. However, given the safety and blood brain barrier permeability of vitamin D 2, we propose that vitamin D 2 may be a suitable agent to target PrP(c) in the brain and therefore is a potential therapeutic candidate for prion disease.
authors.affiliation: Department of Medical Pharmacology; Faculty of Pharmaceutical Sciences; Tokushima Bunri University; Yamashiro-cho, Tokushima, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Suenaga
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hiramoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsunaga
mesh_terms: D019286:Endopeptidase K / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004872:Ergocalciferols / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D018621:PrPC Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000939:Epitopes; D004872:Ergocalciferols; D018621:PrPC Proteins; D011994:Recombinant Proteins; D019286:Endopeptidase K
keywords: PrPc; PrPsc; oligomerization; prion disease; vitamin D2