{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:32:02Z","timestamp":1792715522856,"version":"4.5.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2016,9,29]],"date-time":"2016-09-29T00:00:00Z","timestamp":1475107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,10,15]],"date-time":"2016-10-15T00:00:00Z","timestamp":1476489600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            \u03b1-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 \u03b1-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\n            <jats:sup>+\/\u2212<\/jats:sup>\n            :\n            <jats:italic>Gfap<\/jats:italic>\n            -luc\n            <jats:sup>+\/\u2212<\/jats:sup>\n            ) mice, which express the A53T mutant of human \u03b1-synuclein and firefly luciferase. After a single intraperitoneal injection with \u03b1-synuclein fibrils, four of five mice developed paralysis and \u03b1-synuclein pathology in the central nervous system, with a median incubation time of 229 \u00b1 17 days. Diseased mice accumulated aggregates of Sarkosyl-insoluble and phosphorylated \u03b1-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 \u03b1-synuclein pathology in the central nervous system after intraglossal injection with \u03b1-synuclein fibrils, after 285 days. These findings are novel and important because they show that, similar to prions, \u03b1-synuclein prionoids can neuroinvade the central nervous system after intraperitoneal or intraglossal injection and can cause neuropathology and disease.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Synucleinopathies are neurodegenerative diseases that are characterized by the pathological presence of aggregated \u03b1-synuclein in cells of the nervous system. Previous studies have shown that \u03b1-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 \u03b1-synuclein can behave similarly to prions. Here we show that \u03b1-synuclein inoculation into the peritoneal cavity or the tongue in mice overexpressing \u03b1-synuclein causes neurodegeneration after neuroinvasion from the periphery, which further corroborates the prionoid character of misfolded \u03b1-synuclein.\n          <\/jats:p>","DOI":"10.1128\/jvi.01399-16","type":"journal-article","created":{"date-parts":[[2016,8,4]],"date-time":"2016-08-04T01:58:51Z","timestamp":1470275931000},"page":"9182-9193","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":93,"title":["Neuroinvasion of \u03b1-Synuclein Prionoids after Intraperitoneal and Intraglossal Inoculation"],"prefix":"10.1128","volume":"90","author":[{"given":"Sara","family":"Breid","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria 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