000077147 001__ 77147
000077147 005__ 20240104111813.0
000077147 0247_ $$2doi$$a10.1038/s41598-019-38500-2
000077147 0248_ $$2sideral$$a109898
000077147 037__ $$aART-2019-109898
000077147 041__ $$aeng
000077147 100__ $$0(orcid)0000-0003-2454-2114$$aLópez-Pérez, Óscar
000077147 245__ $$aDysregulation of autophagy in the central nervous system of sheep naturally infected with classical scrapie
000077147 260__ $$c2019
000077147 5060_ $$aAccess copy available to the general public$$fUnrestricted
000077147 5203_ $$aAutophagy is a dynamic cellular mechanism involved in protein and organelle turnover through lysosomal degradation. Autophagy regulation modulates the pathologies associated with many neurodegenerative diseases. Using sheep naturally infected with scrapie as a natural animal model of prion diseases, we investigated the regulation of autophagy in the central nervous system (CNS) during the clinical phase of the disease. We present a gene expression and protein distribution analysis of different autophagy-related markers and investigate their relationship with prion-associated lesions in several areas of the CNS. Gene expression of autophagy markers ATG5 and ATG9 was downregulated in some areas of scrapie brains. In contrast, ATG5 protein accumulates in medulla oblongata and positively correlates with prion deposition and scrapie-related lesions. The accumulation of this protein and p62, a marker of autophagy impairment, suggests that autophagy is decreased in the late phases of the disease. However, the increment of LC3 proteins and the mild expression of p62 in basal ganglia and cerebellum, primarily in Purkinje cells, suggests that autophagy machinery is still intact in less affected areas. We hypothesize that specific cell populations of the CNS may display neuroprotective mechanisms against prion-induced toxicity through the induction of PrPSc clearance by autophagy.
000077147 536__ $$9info:eu-repo/grantAgreement/ES/DGA/A19-17R$$9info:eu-repo/grantAgreement/ES/DGA/C012-2014$$9info:eu-repo/grantAgreement/ES/DGA/C020-2014$$9info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67945-P
000077147 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000077147 590__ $$a3.998$$b2019
000077147 591__ $$aMULTIDISCIPLINARY SCIENCES$$b17 / 71 = 0.239$$c2019$$dQ1$$eT1
000077147 592__ $$a1.341$$b2019
000077147 593__ $$aMultidisciplinary$$c2019$$dQ1
000077147 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000077147 700__ $$0(orcid)0000-0001-9075-2764$$aOtero, Alicia
000077147 700__ $$0(orcid)0000-0003-3352-740X$$aFilali, Hicham$$uUniversidad de Zaragoza
000077147 700__ $$0(orcid)0000-0002-5228-248X$$aSanz-Rubio, David
000077147 700__ $$0(orcid)0000-0002-7243-1737$$aToivonen, Janne M.$$uUniversidad de Zaragoza
000077147 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza, Pilar$$uUniversidad de Zaragoza
000077147 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola, Juan J.$$uUniversidad de Zaragoza
000077147 700__ $$0(orcid)0000-0002-2746-3932$$aBolea, Rosa$$uUniversidad de Zaragoza
000077147 700__ $$0(orcid)0000-0001-6016-4726$$aMartín-Burriel, Inmaculada$$uUniversidad de Zaragoza
000077147 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000077147 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000077147 773__ $$g9 (2019), 1911 [14 pp.]$$pSci. rep. (Nat. Publ. Group)$$tScientific reports (Nature Publishing Group)$$x2045-2322
000077147 8564_ $$s4282123$$uhttps://zaguan.unizar.es/record/77147/files/texto_completo.pdf$$yVersión publicada
000077147 8564_ $$s112375$$uhttps://zaguan.unizar.es/record/77147/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000077147 909CO $$ooai:zaguan.unizar.es:77147$$particulos$$pdriver
000077147 951__ $$a2024-01-04-11:03:07
000077147 980__ $$aARTICLE