{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:05:32Z","timestamp":1760144732235,"version":"build-2065373602"},"reference-count":95,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"USPHS","award":["2R44NS108804"],"award-info":[{"award-number":["2R44NS108804"]}]},{"name":"The Charles D Lucas, Jr. Professorship for Parkinson\u2019s Disease Research at the University of Kentucky","award":["2R44NS108804"],"award-info":[{"award-number":["2R44NS108804"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Applied Biosciences"],"abstract":"<jats:p>Synucleinopathies, typified by Parkinson\u2019s disease (PD), entail the accumulation of \u03b1-synuclein (\u03b1Syn) aggregates in nerve cells. Various \u03b1Syn mutants, including the \u03b1Syn A53T variant linked to early-onset PD, increase the propensity for \u03b1Syn aggregate formation. In addition to disrupting protein homeostasis and inducing proteostatic stress, the aggregation of \u03b1Syn in PD is associated with an imbalance in iron metabolism, which increases the generation of reactive oxygen species and causes oxidative stress. This study explored the impact of \u03b1Syn A53T expression in transgenic hairy roots of four medicinal plants (Lobelia cardinalis, Artemisia annua, Salvia miltiorrhiza, and Polygonum multiflorum). In all tested plants, \u03b1Syn A53T expression triggered proteotoxic stress and perturbed iron homeostasis, mirroring the molecular profile observed in human and animal nerve cells. In addition to the common eukaryotic defense mechanisms against proteostatic and oxidative stresses, a plant stress response generally includes the biosynthesis of a diverse set of protective secondary metabolites. Therefore, the hairy root cultures expressing \u03b1Syn A53T offer a platform for identifying secondary metabolites that can ameliorate the effects of \u03b1Syn, thereby aiding in the development of possible PD treatments and\/or treatments of synucleinopathies.<\/jats:p>","DOI":"10.3390\/applbiosci3020016","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T05:40:47Z","timestamp":1716270047000},"page":"233-249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Plant Model of \u03b1-Synucleinopathy: Expression of \u03b1-Synuclein A53T Variant in Hairy Root Cultures Leads to Proteostatic Stress and Dysregulation of Iron Metabolism"],"prefix":"10.3390","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3061-6968","authenticated-orcid":false,"given":"Jasmina","family":"Kurepa","sequence":"first","affiliation":[{"name":"Department of Plant and Soil Sciences, Martin-Gatton College of Agriculture Food and Environment, Kentucky Tobacco Research & Development Center, University of Kentucky, Lexington, KY 40546, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen A.","family":"Bruce","sequence":"additional","affiliation":[{"name":"Naprogenix, Inc.\u2122, UK-AsTeCC, 145 Graham Avenue, Lexington, KY 40506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg A.","family":"Gerhardt","sequence":"additional","affiliation":[{"name":"Brain Restoration Center, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Department of Neurosurgery, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Department of Neuroscience, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Department of Neurology, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-4619","authenticated-orcid":false,"given":"Jan A.","family":"Smalle","sequence":"additional","affiliation":[{"name":"Department of Plant and Soil Sciences, Martin-Gatton College of Agriculture Food and Environment, Kentucky Tobacco Research & Development Center, University of Kentucky, Lexington, KY 40546, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a009399","DOI":"10.1101\/cshperspect.a009399","article-title":"\u03b1-Synuclein in Parkinson\u2019s disease","volume":"2","author":"Stefanis","year":"2012","journal-title":"Cold Spring Harb. 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