000070709 001__ 70709
000070709 005__ 20220208112846.0
000070709 0247_ $$2doi$$a10.1128/JVI.01399-16
000070709 0248_ $$2sideral$$a106053
000070709 037__ $$aART-2016-106053
000070709 041__ $$aeng
000070709 100__ $$aBreid, S.
000070709 245__ $$aNeuroinvasion of alpha-Synuclein Prionoids after Intraperitoneal and Intraglossal Inoculation
000070709 260__ $$c2016
000070709 5060_ $$aAccess copy available to the general public$$fUnrestricted
000070709 5203_ $$aalpha-Synuclein is a soluble, cellular protein that in a number of neurodegenerative diseases, including Parkinson''s disease and multiple system atrophy, forms pathological deposits of protein aggregates. Because misfolded alpha-synuclein has some characteristics that resemble those of prions, we investigated its potential to induce disease after intraperitoneal or intraglossal challenge injection into bigenic Tg(M83(+/-):Gfap-luc(+/-)) mice, which express the A53T mutant of human alpha-synuclein and firefly luciferase. After a single intraperitoneal injection with alpha-synuclein fibrils, four of five mice developed paralysis and alpha-synuclein pathology in the central nervous system, with a median incubation time of 229 +/- 17 days. Diseased mice accumulated aggregates of Sarkosyl-insoluble and phosphorylated alpha-synuclein in the brain and spinal cord, which colocalized with ubiquitin and p62 and were accompanied by gliosis. In contrast, only one of five mice developed alpha-synuclein pathology in the central nervous system after intraglossal injection with alpha-synuclein fibrils, after 285 days. These findings are novel and important because they show that, similar to prions, alpha-synuclein prionoids can neuroinvade the central nervous system after intraperitoneal or intraglossal injection and can cause neuropathology and disease. IMPORTANCE Synucleinopathies are neurodegenerative diseases that are characterized by the pathological presence of aggregated alpha-synuclein in cells of the nervous system. Previous studies have shown that alpha-synuclein aggregates made of recombinant protein or derived from brains of patients can spread in the central nervous system in a spatiotemporal manner when inoculated into the brains of animals and can induce pathology and neurologic disease, suggesting that misfolded alpha-synuclein can behave similarly to prions. Here we show that alpha-synuclein inoculation into the peritoneal cavity or the tongue in mice overexpressing alpha-synuclein causes neurodegeneration after neuroinvasion from the periphery, which further corroborates the prionoid character of misfolded alpha-synuclein.
000070709 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000070709 590__ $$a4.663$$b2016
000070709 591__ $$aVIROLOGY$$b6 / 33 = 0.182$$c2016$$dQ1$$eT1
000070709 592__ $$a3.113$$b2016
000070709 593__ $$aImmunology$$c2016$$dQ1
000070709 593__ $$aVirology$$c2016$$dQ1
000070709 593__ $$aMicrobiology$$c2016$$dQ1
000070709 593__ $$aInsect Science$$c2016$$dQ1
000070709 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000070709 700__ $$aBernis, M.E.
000070709 700__ $$aBabila, J.T.
000070709 700__ $$0(orcid)0000-0001-7098-2327$$aGarza, M.C.$$uUniversidad de Zaragoza
000070709 700__ $$aWille, H.
000070709 700__ $$aTamguney, G.
000070709 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000070709 773__ $$g90, 20 (2016), 9182-9193$$pJ. virol.$$tJournal of virology$$x0022-538X
000070709 8564_ $$s985712$$uhttps://zaguan.unizar.es/record/70709/files/texto_completo.pdf$$yVersión publicada
000070709 8564_ $$s126862$$uhttps://zaguan.unizar.es/record/70709/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000070709 909CO $$ooai:zaguan.unizar.es:70709$$particulos$$pdriver
000070709 951__ $$a2022-02-08-11:23:57
000070709 980__ $$aARTICLE