{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T09:20:20Z","timestamp":1760347220826,"version":"3.44.0"},"reference-count":76,"publisher":"The Company of Biologists","issue":"8","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008222","name":"Ben and Catherine Ivy Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008222","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012807","name":"Midwestern University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012807","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Sexual dimorphism in Parkinson's disease (PD) pathophysiology is poorly understood. Elucidating consequences of disease-causing mutations on brain redox chemistry may reveal therapeutic targets for all people with PD. We report that male Drosophila had increased hydrogen peroxide and glutathione (G-SH) redox disequilibrium in vulnerable dopaminergic neuron mitochondria. Levels of cysteine and oxidized cystine were decreased, with cysteine\/cystine ratios (indicating less oxidative stress) and G-SH levels being elevated in parkin-null (park\u2212\/\u2212) Drosophila brains, and more so in males. We report effects of parkin loss and sex on the levels of low-molecular-weight thiols involved in G-SH synthesis, providing clues as to mechanisms implicated in altered levels of brain G-SH, cysteine and cystine. Protein nitration was decreased in the brain of park\u2212\/\u2212 flies, especially in females, suggesting that decreased nitric oxide levels compensate for loss of parkin or lack of protective nitric oxide synthase activity. Our results imply that park\u2212\/\u2212 flies have elevated levels of G-SH that meet antioxidant demand in the absence of parkin in the whole brain, but not in vulnerable neurons. Identification of sexually dimorphic PD risk factors could inform symptom management and highlight sex-specific therapeutic strategies.<\/jats:p>","DOI":"10.1242\/dmm.052250","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T07:57:14Z","timestamp":1755590234000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>park+\/+<\/i> and <i>park\u2212\/\u2212 Drosophila<\/i> have sexually dimorphic brain redox chemistry"],"prefix":"10.1242","volume":"18","author":[{"given":"Amber N.","family":"Juba","sequence":"first","affiliation":[{"name":"Midwestern University 1 Biomedical Sciences Program , , Glendale, AZ 85308 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bobbi","family":"Stwalley","sequence":"additional","affiliation":[{"name":"Midwestern University 1 Biomedical Sciences Program , , Glendale, AZ 85308 ,","place":["USA"]},{"name":"Department of Anatomy, Arizona College of Osteopathic Medicine, Midwestern University 2 , Glendale, AZ 85308 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tigran","family":"Margaryan","sequence":"additional","affiliation":[{"name":"Ivy Brain Tumor Center at Barrow Neurological Institute 3 Department of Translational Neuroscience , , Phoenix, AZ 85013 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riley","family":"Hamel","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Arizona College of Osteopathic Medicine, Midwestern University 2 , Glendale, AZ 85308 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda N.","family":"Foley","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Arizona College of Osteopathic Medicine, Midwestern University 2 , Glendale, AZ 85308 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. 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