{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:24:48Z","timestamp":1789842288188,"version":"4.0.1"},"reference-count":67,"publisher":"The Royal Society","issue":"1306","license":[{"start":{"date-parts":[[1994,3,29]],"date-time":"1994-03-29T00:00:00Z","timestamp":764899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1994,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>An abnormally protease-resistant and apparently neuropathogenic form of PrP accumulates in the brains of hosts with scrapie and related transmissible spongiform encephalopathies. Studies with scrapieinfected neuroblastom a cells have highlighted dramatic differences in the metabolism of the normal (protease-sensitive) and scrapie-associated (protease-resistant) isoforms of PrP. Furthermore, this model has been useful in identifying inhibitors of protease-resistant PrP accumulation and scrapie agent replication which are valuable as potential therapeutic agents and as probes of the mechanism of protease-resistant PrP formation. These inhibitors include the amyloid stain Congo red and certain sulphated glycans which are glycosaminoglycans themselves or glycosaminoglycan analogues. The relative potencies of various sulphated glycans correlate with their previously determ ined anti-scrapie activities in vivo, suggesting that the prophylactic effects of sulphated polyanions is due to inhibition of protease-resistant PrP accumulation. These and other observations suggest that an interaction of PrP with endogenous sulphated glycosaminoglycans or proteoglycans is important in protease-resistant PrP accumulation, and raise the possibility that therapies for transmissible spongiform encephalopathies and other amyloidoses could be based on blocking (pre)am yloid-glycosaminoglycan interactions.<\/jats:p>","DOI":"10.1098\/rstb.1994.0035","type":"journal-article","created":{"date-parts":[[2006,12,15]],"date-time":"2006-12-15T17:54:58Z","timestamp":1166205298000},"page":"399-404","source":"Crossref","is-referenced-by-count":17,"title":["Scrapie-associated PrP accumulation and agent replication: effects of sulphated glycosaminoglycan analogues"],"prefix":"10.1098","volume":"343","author":[{"given":"Byron","family":"Caughey","sequence":"first","affiliation":[{"name":"Laboratory of Persistent Viral Diseases, NIH Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, Hamilton, Montana 59840, U. S. A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","reference":[{"key":"p_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90662-8"},{"key":"p_2","doi-asserted-by":"publisher","DOI":"10.1038\/310418a0"},{"key":"p_3","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.1.149"},{"key":"p_4","doi-asserted-by":"publisher","DOI":"10.1126\/science.6815801"},{"key":"p_5","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(87)90380-8"},{"key":"p_6","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.110.3.743"},{"key":"p_7","first-page":"16188","article-title":"E vidence for synthesis o f scrapie p rion p ro tein in the endocytic p athw ay. J . biol","volume":"267","author":"Prusiner S.B.","year":"1992","journal-title":"Chem."},{"key":"p_8","doi-asserted-by":"publisher","DOI":"10.1038\/356577a0"},{"key":"p_9","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90360-3"},{"key":"p_10","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90225-4"},{"key":"p_11","first-page":"860","article-title":"Scrapie associated P rP accu m u latio n an d its prevention: insights from cell culture. Br. med","volume":"49","year":"1993","journal-title":"Bull."},{"key":"p_12","unstructured":"C aughey B. Brow n K . R ay m o n d G .J. K atzenstein G .E. form o f P rP (prion protease) to sulfated glycosam inoglycan an d C ongo red. J . Virol. (In the press.)"},{"key":"p_13","first-page":"768","article-title":"P oten t in h ib itio n of scrapie-associated P rP ac cu m u latio n by C ongo red. J","volume":"59","year":"1992","journal-title":"Neurochem."},{"key":"p_14","first-page":"18217","article-title":"T h e scrapie-associated form of P rP is m ade from a cell surface p recu rso r th a t is b oth protease- an d phospholipase-sensitive. J . biol","volume":"266","year":"1991","journal-title":"Chem."},{"key":"p_15","doi-asserted-by":"crossref","unstructured":"C au g h ey B. & R ay m o n d G .J. 1993 Sulfated polyanion in h ib itio n of scrapie-associated P rP accu m u latio n in cu ltu red cells. J .Virol. 67 643-650.","DOI":"10.1128\/JVI.67.2.643-650.1993"},{"key":"p_16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.13.4657"},{"key":"p_17","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1128\/JVI.63.1.175-181.1989","article-title":"Prion protein (PrP) biosynthesis in scrapie-infected an d uninfected neuro b lasto m a cells. J","volume":"63","author":"Buchm M .","year":"1989","journal-title":"Virol."},{"key":"p_18","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1128\/JVI.64.3.1093-1101.1990","article-title":"N orm al and scrapie-associated forms of prion protein differ in th eir sensitivities to phospholipase and proteases in in ta ct n eu ro b lasto m a cells. J","volume":"64","author":"Buller R .","year":"1990","journal-title":"Virol."},{"key":"p_19","doi-asserted-by":"publisher","DOI":"10.1021\/bi00245a003"},{"key":"p_20","doi-asserted-by":"crossref","first-page":"6597","DOI":"10.1128\/JVI.65.12.6597-6603.1991","article-title":"6 N -term inal tru n ca tio n of the scrapie-associated form of P rP by Iysosomal protease(s): im plications reg a rd - ing the site of conversion of P rP to the protease-resistant state. J","volume":"65","year":"1991","journal-title":"Virol."},{"key":"p_21","doi-asserted-by":"crossref","first-page":"6270","DOI":"10.1128\/JVI.67.10.6270-6272.1993","article-title":"C ongo red in h ibition of scrapie agent replication. J","volume":"67","year":"1993","journal-title":"Virol."},{"key":"p_22","doi-asserted-by":"publisher","DOI":"10.1038\/315331a0"},{"key":"p_23","first-page":"243","article-title":"A ntibody to scrapie-associated fibril p ro - tein identifies a cellular antigen. J . gen","volume":"67","author":"Cho H .","year":"1986","journal-title":"Virol."},{"key":"p_24","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.37.8.1271"},{"key":"p_25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.2.375"},{"key":"p_26","first-page":"457","article-title":"C hem oprophylaxis of scrapie in mice. J . gen","volume":"72","author":"Ehlers B.","year":"1991","journal-title":"Virol."},{"key":"p_27","doi-asserted-by":"publisher","DOI":"10.1038\/306476a0"},{"key":"p_28","first-page":"1325","article-title":"D extran sulphate 500 delays and prevents mouse scrapie by im pairm en t of agent replication in spleen. J . gen","volume":"65","author":"Ehlers B.","year":"1984","journal-title":"Virol."},{"key":"p_29","first-page":"423","article-title":"T he reticuloendothelial system in scrapie pathogenesis. J . gen","volume":"65","author":"Ehlers B.","year":"1984","journal-title":"Virol."},{"key":"p_30","doi-asserted-by":"publisher","DOI":"10.1021\/bi00447a017"},{"key":"p_31","first-page":"463","article-title":"Prolongation of scrapie incubation period by an injection of dextran sulphate 500 w ithin the m onth before or after infection. .\/. gen","volume":"67","author":"Dickinson A.G.","year":"1986","journal-title":"Virol."},{"key":"p_32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.10940"},{"key":"p_33","doi-asserted-by":"publisher","DOI":"10.1038\/2151043a0"},{"key":"p_34","first-page":"69","article-title":"F ibril-derived am y - loid en h an cin g factor as n u cleatin g agents in A Izheim er's disease an d transm issible virus d em en tia","volume":"5","year":"1989","journal-title":"Neurosci."},{"key":"p_35","doi-asserted-by":"crossref","unstructured":"G uiroy D .C . Y an a g ih ara R. & G ajdusek D .C . 1991 L ocalization o f am yloidogenic proteins an d sulfated glycosam inoglycans in nontransm issible an d transm issible cerebral am yloidoses. Acta neuropath. 82 87-92.","DOI":"10.1007\/BF00293949"},{"key":"p_36","doi-asserted-by":"publisher","DOI":"10.1021\/bi00055a003"},{"key":"p_37","first-page":"2591","article-title":"T h e m ajor polypeptide of scrapie-associated fibrils (SAF) has the sam e size, charge d istrib u tio n an d N -term in al protein sequence as pred icted for the norm al b rain p rotein (PrP)","volume":"5","author":"Ith G.","year":"1986","journal-title":"E M B O J ."},{"key":"p_38","first-page":"106","article-title":"Infection specific prion protein (PrP) accum ulates on n eu ro n al plasm alem m a in scrapie infected mice. Neurosci","volume":"147","author":"Jeffrey M .","year":"1992","journal-title":"Lett."},{"key":"p_39","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.30.3.409"},{"key":"p_40","doi-asserted-by":"publisher","DOI":"10.1139\/y87-282"},{"key":"p_41","first-page":"661","article-title":"S u Ip h ate polyanions prolong the in cu b atio n period of scrapie-infected ham sters. J . gen","volume":"73","author":"Casaccia P.","year":"1992","journal-title":"Virol."},{"key":"p_42","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711660404"},{"key":"p_43","first-page":"363","article-title":"D evelopm ental expression and regional distribution of the scrapie-associated protein m R N A in the ra t central nervous system","volume":"417","year":"1992","journal-title":"Brain Res."},{"key":"p_44","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1242\/dev.115.1.117","article-title":"T h e prion protein gene: a role in mouse embryogenesis","volume":"115","author":"Bride P.","year":"1992","journal-title":"Development"},{"key":"p_45","first-page":"622","article-title":"U Itrastru c tu ral localization of scrapie prion proteins in cytoplasm ic vesicles of infected cultured cells","volume":"65","year":"1991","journal-title":"Lab. Invest."},{"key":"p_46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.8.2310"},{"key":"p_47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.24.9811"},{"key":"p_48","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(85)90333-2"},{"key":"p_49","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.40.3_Part_1.518"},{"key":"p_50","doi-asserted-by":"publisher","DOI":"10.1126\/science.6801762"},{"key":"p_51","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1128\/JVI.62.8.2845-2849.1988","article-title":"Analysis of frequency o f infection, specific infectivity, and prion protein biosynthesis in scrapie-infected neuroblastom a cell clones. J","volume":"62","author":"Race R .","year":"1988","journal-title":"Virol"},{"key":"p_52","first-page":"1391","article-title":"C h a ra c te rization of scrapie infection in mouse n euroblasto m a cells. J. gen","volume":"68","author":"Fadness L .","year":"1987","journal-title":"Virol."},{"key":"p_53","first-page":"3319","article-title":"D etection of proteinase K - resistant prion protein and infectivity in mouse spleen by 2 weeks after scrapie agent inoculation. J . gen","volume":"73","author":"Race R .","year":"1992","journal-title":"Virol."},{"key":"p_54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.17.6377"},{"key":"p_55","first-page":"671","article-title":"D etection of scrapie-associated fibril (SAF) proteins using anti-SA F an tibody in non-purified tissue p rep aratio n s. J . gen","volume":"67","year":"1986","journal-title":"Virol."},{"key":"p_56","first-page":"29","article-title":"Scrapie-infected spleens: analysis of infectivity, scrapieassociated fibrils, and protease-resistant proteins. J . infect","volume":"164","year":"1991","journal-title":"Dis."},{"key":"p_57","first-page":"488","article-title":"Differences in the m em brane interaction o f scrapie am yloid precursor proteins in norm al and scrapie- or C reutzfeldt-Jakob disease-infected brains. J . infect","volume":"163","author":"Safar J .","year":"1991","journal-title":"Dis."},{"key":"p_58","first-page":"1745","article-title":"Im m u n o reactiv ity of a synthetic p en tad ecap ep tid e corresponding to the N -term inal region of the scrapie prion protein. J . gen","volume":"67","author":"Doi S.","year":"1986","journal-title":"Virol."},{"key":"p_59","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(89)90108-5"},{"key":"p_60","doi-asserted-by":"crossref","unstructured":"Snow A .D . Kisilevsky R . W illm er J . P rusiner S.B. & D eA rm ond S.J. 1989 Sulfated glycosam inoglycans in am yloid plaques o f prion diseases. Acta neuropathol. 77 337-342.","DOI":"10.1007\/BF00687367"},{"key":"p_61","first-page":"601","article-title":"Im m u n o - localization o f h ep a rin sulfate proteoglycans to the prion pro tein am yloid p laques of G erstm an n -S trau ssler S yndrom e, C reu tzfeld t-Ja k o b disease an d scrapie","volume":"63","author":"Snow A .","year":"1990","journal-title":"Lab. Invest."},{"key":"p_62","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90150-4"},{"key":"p_63","doi-asserted-by":"publisher","DOI":"10.1021\/bi00490a001"},{"key":"p_64","doi-asserted-by":"publisher","DOI":"10.1021\/bi00474a028"},{"key":"p_65","doi-asserted-by":"publisher","DOI":"10.1021\/bi00059a016"},{"key":"p_66","first-page":"1398","article-title":"A soluble form o f p rio n p ro tein in h u m a n cerebrospinal fluid: Im p licatio n s for prionrelated encephalopathies. Biochem. biophys","volume":"184","author":"Prelli F.","year":"1992","journal-title":"Res. Commun."},{"key":"p_67","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.3.8.851"}],"container-title":["Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.1994.0035","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/rstb\/article-pdf\/343\/1306\/399\/83160\/rstb.1994.0035.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/royalsocietypublishing.org\/rstb\/article-pdf\/343\/1306\/399\/83160\/rstb.1994.0035.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:17:36Z","timestamp":1767356256000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/rstb\/article\/343\/1306\/399\/18560\/Scrapie-associated-PrP-accumulation-and-agent"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,3,29]]},"references-count":67,"journal-issue":{"issue":"1306","published-print":{"date-parts":[[1994,3,29]]}},"URL":"https:\/\/doi.org\/10.1098\/rstb.1994.0035","relation":{},"ISSN":["0962-8436","1471-2970"],"issn-type":[{"value":"0962-8436","type":"print"},{"value":"1471-2970","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,3,29]]}}}