000098393 001__ 98393
000098393 005__ 20230519145349.0
000098393 0247_ $$2doi$$a10.3390/ijms22010465
000098393 0248_ $$2sideral$$a121431
000098393 037__ $$aART-2021-121431
000098393 041__ $$aeng
000098393 100__ $$0(orcid)0000-0001-9075-2764$$aOtero, Alicia$$uUniversidad de Zaragoza
000098393 245__ $$aPrion-associated neurodegeneration causes both endoplasmic reticulum stress and proteasome impairment in a murine model of spontaneous disease
000098393 260__ $$c2021
000098393 5060_ $$aAccess copy available to the general public$$fUnrestricted
000098393 5203_ $$aPrion diseases are a group of neurodegenerative disorders that can be spontaneous, familial or acquired by infection. Conversion of prion protein PrPC to its abnormal and misfolded isoform PrPSc is the main event in the pathogenesis of prion diseases of all origins. In spontaneous prion diseases, the mechanisms that trigger the formation of PrPSc in the central nervous system, remain unknown. Several reports have demonstrated that the accumulation of PrPSc can induce endoplasmic reticulum (ER) stress and proteasome impairment from early stages of the prion disease. Both mechanisms lead to an increment of PrP aggregates in the secretory pathway, which could explain the pathogenesis of spontaneous prion diseases. Here, we investigate the role of ER stress and proteasome impairment during prion disorders in a murine model of spontaneous prion disease (TgVole) coexpressing the UbG76V-GFP reporter, which allows measuring the proteasome activity in vivo. Spontaneously prion-affected mice showed a significantly higher accumulation of the PKR-like ER kinase (PERK), the ER chaperone binding immunoglobulin protein (BiP/Grp78), the ER protein disulfide isomerase (PDI) and the UbG76V-GFP reporter than age-matched controls in certain brain areas. Upregulation of PERK, BiP, PDI and ubiquitin was detected from the preclinical stage of the disease, indicating that ER stress and proteasome impairment begin at early stages of the spontaneous disease. Strong correlations were found between the deposition of these markers and neuropathological markers of prion disease in both preclinical and clinical mice. Our results suggest that both ER stress and proteasome impairment occur during the pathogenesis of spontaneous prion diseases.
000098393 536__ $$9info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/EFA-148-16 REDPRION$$9info:eu-repo/grantAgreement/EUR/INTERREG-V-A-POCTEFA-2014-2020$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/RTI2018-096322-B-I00$$9info:eu-repo/grantAgreement/ES/MINECO/SEV-2016-0644
000098393 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000098393 590__ $$a6.208$$b2021
000098393 592__ $$a1.176$$b2021
000098393 594__ $$a6.9$$b2021
000098393 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b69 / 297 = 0.232$$c2021$$dQ1$$eT1
000098393 593__ $$aComputer Science Applications$$c2021$$dQ1
000098393 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b50 / 180 = 0.278$$c2021$$dQ2$$eT1
000098393 593__ $$aInorganic Chemistry$$c2021$$dQ1
000098393 593__ $$aSpectroscopy$$c2021$$dQ1
000098393 593__ $$aOrganic Chemistry$$c2021$$dQ1
000098393 593__ $$aPhysical and Theoretical Chemistry$$c2021$$dQ1
000098393 593__ $$aMolecular Biology$$c2021$$dQ1
000098393 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000098393 700__ $$0(orcid)0000-0002-0388-9429$$aBetancor, Marina$$uUniversidad de Zaragoza
000098393 700__ $$aEraña, Hasier
000098393 700__ $$aFernández Borges, Natalia
000098393 700__ $$aLucas, José Javier
000098393 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola, Juan José$$uUniversidad de Zaragoza
000098393 700__ $$aCastilla, Joaquín
000098393 700__ $$0(orcid)0000-0002-2746-3932$$aBolea, Rosa$$uUniversidad de Zaragoza
000098393 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000098393 773__ $$g22, 1 (2021), Art. 465 [21 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000098393 8564_ $$s4041585$$uhttps://zaguan.unizar.es/record/98393/files/texto_completo.pdf$$yVersión publicada
000098393 8564_ $$s2681440$$uhttps://zaguan.unizar.es/record/98393/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000098393 909CO $$ooai:zaguan.unizar.es:98393$$particulos$$pdriver
000098393 951__ $$a2023-05-18-13:25:07
000098393 980__ $$aARTICLE