000129553 001__ 129553
000129553 005__ 20241125101122.0
000129553 0247_ $$2doi$$a10.3390/ijms242417525
000129553 0248_ $$2sideral$$a135855
000129553 037__ $$aART-2023-135855
000129553 041__ $$aeng
000129553 100__ $$0(orcid)0000-0001-7098-2327$$aGarza, M. Carmen$$uUniversidad de Zaragoza
000129553 245__ $$aIn vitro and in vivo evidence towards fibronectin’s protective effects against prion infection
000129553 260__ $$c2023
000129553 5060_ $$aAccess copy available to the general public$$fUnrestricted
000129553 5203_ $$aA distinctive signature of the prion diseases is the accumulation of the pathogenic isoform of the prion protein, PrPSc, in the central nervous system of prion-affected humans and animals. PrPSc is also found in peripheral tissues, raising concerns about the potential transmission of pathogenic prions through human food supplies and posing a significant risk to public health. Although muscle tissues are considered to contain levels of low prion infectivity, it has been shown that myotubes in culture efficiently propagate PrPSc. Given the high consumption of muscle tissue, it is important to understand what factors could influence the establishment of a prion infection in muscle tissue. Here we used in vitro myotube cultures, differentiated from the C2C12 myoblast cell line (dC2C12), to identify factors affecting prion replication. A range of experimental conditions revealed that PrPSc is tightly associated with proteins found in the systemic extracellular matrix, mostly fibronectin (FN). The interaction of PrPSc with FN decreased prion infectivity, as determined by standard scrapie cell assay. Interestingly, the prion-resistant reserve cells in dC2C12 cultures displayed a FN-rich extracellular matrix while the prion-susceptible myotubes expressed FN at a low level. In agreement with the in vitro results, immunohistopathological analyses of tissues from sheep infected with natural scrapie demonstrated a prion susceptibility phenotype linked to an extracellular matrix with undetectable levels of FN. Conversely, PrPSc deposits were not observed in tissues expressing FN. These data indicate that extracellular FN may act as a natural barrier against prion replication and that the extracellular matrix composition may be a crucial feature determining prion tropism in different tissues.
000129553 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000129553 590__ $$a4.9$$b2023
000129553 592__ $$a1.179$$b2023
000129553 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b66 / 313 = 0.211$$c2023$$dQ1$$eT1
000129553 593__ $$aMedicine (miscellaneous)$$c2023$$dQ1
000129553 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b68 / 231 = 0.294$$c2023$$dQ2$$eT1
000129553 593__ $$aPhysical and Theoretical Chemistry$$c2023$$dQ1
000129553 593__ $$aComputer Science Applications$$c2023$$dQ1
000129553 593__ $$aInorganic Chemistry$$c2023$$dQ1
000129553 593__ $$aSpectroscopy$$c2023$$dQ1
000129553 593__ $$aOrganic Chemistry$$c2023$$dQ1
000129553 593__ $$aMolecular Biology$$c2023$$dQ2
000129553 593__ $$aCatalysis$$c2023$$dQ2
000129553 594__ $$a8.1$$b2023
000129553 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000129553 700__ $$aKang, Sang-Gyun
000129553 700__ $$aKim, Chiye
000129553 700__ $$0(orcid)0000-0002-7453-1766$$aMonleón, Eva$$uUniversidad de Zaragoza
000129553 700__ $$avan der Merwe, Jacques
000129553 700__ $$aKramer, David A.
000129553 700__ $$aFahlman, Richard
000129553 700__ $$aSim, Valerie L.
000129553 700__ $$aAiken, Judd
000129553 700__ $$aMcKenzie, Debbie
000129553 700__ $$aCortez, Leonardo M.
000129553 700__ $$aWille, Holger
000129553 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología
000129553 7102_ $$11003$$2027$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Anatom.Embriol.Humana
000129553 773__ $$g24, 24 [24 pp.] (2023), 17525$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000129553 8564_ $$s6356517$$uhttps://zaguan.unizar.es/record/129553/files/texto_completo.pdf$$yVersión publicada
000129553 8564_ $$s2644123$$uhttps://zaguan.unizar.es/record/129553/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000129553 909CO $$ooai:zaguan.unizar.es:129553$$particulos$$pdriver
000129553 951__ $$a2024-11-22-11:56:56
000129553 980__ $$aARTICLE