{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:04:58Z","timestamp":1789844698450,"version":"4.0.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"The Michael J. Fox Foundation for Parkinson\u2019s Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012479","name":"Weston Brain Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The pathological misfolding and aggregation of soluble \u03b1-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson\u2019s disease, a progressive age-related neurodegenerative disease for which there is no cure.<\/jats:p>\n               <jats:p>HET-s is a soluble fungal protein that can form assembled amyloid fibrils in its prion state. We engineered HET-s(218\u2013298) to form four different fibrillar vaccine candidates, each displaying a specific conformational epitope present on the surface of \u03b1-synuclein fibrils. Vaccination with these four vaccine candidates prolonged the survival of immunized TgM83+\/\u2212 mice challenged with \u03b1-synuclein fibrils by 8% when injected into the brain to model brain-first Parkinson\u2019s disease or by 21% and 22% when injected into the peritoneum or gut wall, respectively, to model body-first Parkinson\u2019s disease. Antibodies from fully immunized mice recognized \u03b1-synuclein fibrils and brain homogenates from patients with Parkinson\u2019s disease, dementia with Lewy bodies and multiple system atrophy.<\/jats:p>\n               <jats:p>Conformation-specific vaccines that mimic epitopes present only on the surface of pathological fibrils but not on soluble monomers, hold great promise for protection against Parkinson\u2019s disease, related synucleinopathies and other amyloidogenic protein misfolding disorders.<\/jats:p>","DOI":"10.1093\/brain\/awae061","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T22:29:34Z","timestamp":1709332174000},"page":"1644-1652","source":"Crossref","is-referenced-by-count":14,"title":["Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson\u2019s disease"],"prefix":"10.1093","volume":"147","author":[{"given":"Verena","family":"Pesch","sequence":"first","affiliation":[{"name":"Institut f\u00fcr 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