000088303 001__ 88303
000088303 005__ 20240104111814.0
000088303 0247_ $$2doi$$a10.1038/s41374-019-0312-z
000088303 0248_ $$2sideral$$a113135
000088303 037__ $$aART-2020-113135
000088303 041__ $$aeng
000088303 100__ $$0(orcid)0000-0003-2454-2114$$aLópez-Pérez, Óscar
000088303 245__ $$aImpairment of autophagy in scrapie-infected transgenic mice at the clinical stage
000088303 260__ $$c2020
000088303 5060_ $$aAccess copy available to the general public$$fUnrestricted
000088303 5203_ $$aAutophagy appears to play a role in the etiology and progress of misfolded protein disorders. Although this process is dysregulated in prion diseases, it is unknown whether this impairment is a cause or a consequence of prion neuropathology. The study of autophagy during the progress of the disease could elucidate its role. For this purpose, we have investigated its regulation at different stages of the disease in Tg338 mice, a transgenic murine model that overexpresses the highly susceptible ovine VRQ prion protein allele. Mice were intracerebrally inoculated with mouse adapted classical scrapie and euthanized at the preclinical and clinical stages of the disease. Regulation of autophagy was investigated analyzing the distribution of LC3-B and p62 proteins by immunohistochemistry. Moreover, the expression of genes involved in autophagy regulation was quantified by real-time PCR. LC3-B and p62 proteins were downregulated and upregulated, respectively, in the central nervous system of infected mice with clinical signs of scrapie. Accumulation of p62 correlated with scrapierelated lesions, suggesting an impairment of autophagy in highly prion-affected areas. In addition, Gas5 (growth arrestspecific 5), Atg5 (autophagy-related 5), and Fbxw7 (F-box and WD repeat domain containing 7) transcripts were
downregulated in mesencephalon and cervical spinal cord of the same group of animals. The impairment of autophagic machinery seems to be part of the pathological process of scrapie, but only during the late stage of prion infection. Similarities between Tg338 mice and the natural ovine disease make them a reliable in vivo model to study prion infection and autophagy side by side.
000088303 536__ $$9info:eu-repo/grantAgreement/ES/DGA/A19-17R$$9info:eu-repo/grantAgreement/ES/DGA/C012-2014$$9info:eu-repo/grantAgreement/ES/DGA/C020-2014$$9info:eu-repo/grantAgreement/ES/FIS/PI17-00949$$9info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67945-P
000088303 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000088303 590__ $$a5.662$$b2020
000088303 591__ $$aPATHOLOGY$$b11 / 77 = 0.143$$c2020$$dQ1$$eT1
000088303 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b38 / 140 = 0.271$$c2020$$dQ2$$eT1
000088303 592__ $$a1.542$$b2020
000088303 593__ $$aCell Biology$$c2020$$dQ1
000088303 593__ $$aPathology and Forensic Medicine$$c2020$$dQ1
000088303 593__ $$aMolecular Biology$$c2020$$dQ1
000088303 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000088303 700__ $$0(orcid)0000-0002-7243-1737$$aToivonen, Janne Markus$$uUniversidad de Zaragoza
000088303 700__ $$0(orcid)0000-0001-9075-2764$$aOtero, Alicia$$uUniversidad de Zaragoza
000088303 700__ $$aSolanas, Laura
000088303 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza, Pilar$$uUniversidad de Zaragoza
000088303 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola, Juan José$$uUniversidad de Zaragoza
000088303 700__ $$0(orcid)0000-0001-5687-6704$$aOsta, Rosario$$uUniversidad de Zaragoza
000088303 700__ $$0(orcid)0000-0002-2746-3932$$aBolea, Rosa$$uUniversidad de Zaragoza
000088303 700__ $$0(orcid)0000-0001-6016-4726$$aMartín-Burriel, Inmaculada$$uUniversidad de Zaragoza
000088303 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000088303 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000088303 773__ $$g100, 1 (2020), 52-63$$pLab. invest.$$tLABORATORY INVESTIGATION$$x0023-6837
000088303 8564_ $$s5173212$$uhttps://zaguan.unizar.es/record/88303/files/texto_completo.pdf$$yPostprint
000088303 8564_ $$s161155$$uhttps://zaguan.unizar.es/record/88303/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000088303 909CO $$ooai:zaguan.unizar.es:88303$$particulos$$pdriver
000088303 951__ $$a2024-01-04-11:03:55
000088303 980__ $$aARTICLE