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While \u03b1-syn is thought to play a pathogenic role in horses with PPID, it is unclear if \u03b1-syn is also misfolded in the pars intermedia and could similarly promote self-aggregation and propagation. Consequently, \u03b1-syn was isolated from the pars intermedia from groups of healthy young and aged horses, and aged PPID-afflicted horses. Seeding experiments confirmed the prion-like properties of \u03b1-syn isolated from PPID-afflicted horses. Next, detection of \u03b1-syn fibrils in pars intermedia via transmission electron microscopy (TEM) was exclusive to PPID-afflicted horses. A bank of fragment peptides was designed to further characterize equine \u03b1-syn misfolding. Region 62\u201387 of equine and human \u03b1-syn peptides was found to be most prone to aggregation according to Tango bioinformatic program and kinetics of aggregation via a thioflavin T fluorescence assay. In both species, fragment peptide 62\u201387 is capable of generating mature fibrils as demonstrated by TEM. The combined animal, bioinformatic, and biophysical studies provide evidence that equine \u03b1-syn is misfolded in PPID horses.<\/jats:p>","DOI":"10.1038\/s41598-021-95396-7","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T10:02:56Z","timestamp":1628244176000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1007-9360","authenticated-orcid":false,"given":"Jessica S.","family":"Fortin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley A.","family":"Hetak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsey E.","family":"Duggan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline M.","family":"Burglass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailey B.","family":"Penticoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7728-5409","authenticated-orcid":false,"suffix":"II","given":"Harold C.","family":"Schott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"95396_CR1","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41531-018-0058-0","volume":"4","author":"C Marras","year":"2018","unstructured":"Marras, C. et al. 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