{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:18:22Z","timestamp":1785845902721,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 NS102035"],"award-info":[{"award-number":["U01 NS102035"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Progressive supranuclear palsy (PSP) is a neurodegenerative disorder clinically characterized by progressive postural instability, supranuclear gaze palsy, parkinsonism, and cognitive decline caused by degeneration in specific areas of the brain including globus pallidus (GP), substantia nigra, and subthalamic nucleus. However, the pathogenetic mechanism of PSP remains unclear to date.Unbiased global proteome analysis of patients' brain samples is an important step toward understanding PSP pathogenesis, as proteins serve as workhorses and building blocks of the cell.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we conducted unbiased mass spectrometry\u2010based global proteome analysis of GP samples from 15 PSP patients, 15 Parkinson disease (PD) patients, and 15 healthy control (HC) individuals. To analyze 45 samples, we conducted 5 batches of 11\u2010plex isobaric tandem mass tag (TMT)\u2010based multiplexing experiments. The identified proteins were subjected to statistical analysis, such as a permutation\u2010based statistical analysis in the significance analysis of microarray (SAM) method and bootstrap receiver operating characteristic curve (ROC)\u2010based statistical analysis. Subsequently, we conducted bioinformatics analyses using gene set enrichment analysis, Search Tool for the Retrieval of Interacting Genes\/Proteins (STRING) protein\u2010protein interaction (PPI) analysis, and weighted gene co\u2010expression network analysis (WGCNA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We have identified 10,231 proteins with \u223c1,000 differentially expressed proteins. The gene set enrichment analysis results showed that the PD pathway was the most highly enriched, followed by pathways for oxidative phosphorylation, Alzheimer disease, Huntington disease, and non\u2010alcoholic fatty liver disease (NAFLD) when PSP was compared to HC or PD. Most of the proteins enriched in the gene set enrichment analysis were mitochondrial proteins such as cytochrome c oxidase, NADH dehydrogenase, acyl carrier protein, succinate dehydrogenase, ADP\/ATP translocase, cytochrome b\u2010c1 complex, and\/or ATP synthase. Strikingly, all of the enriched mitochondrial proteins in the PD pathway were downregulated in PSP compared to both HC and PD. The subsequent STRING PPI analysis and the WGCNA further supported that the mitochondrial proteins were the most highly enriched in PSP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study showed that the mitochondrial respiratory electron transport chain complex was the key proteins that were dysregulated in GP of PSP, suggesting that the mitochondrial respiratory electron transport chain complex could potentially be involved in the pathogenesis of PSP. This is the first global proteome analysis of human GP from PSP patients, and this study paves the way to understanding the mechanistic pathogenesis of PSP.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1076","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T11:34:08Z","timestamp":1668080048000},"source":"Crossref","is-referenced-by-count":27,"title":["Mass spectrometry\u2010based proteomics analysis of human globus pallidus from progressive supranuclear palsy patients discovers multiple disease pathways"],"prefix":"10.1002","volume":"12","author":[{"given":"Yura","family":"Jang","sequence":"first","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs Institute for Cell Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thujitha","family":"Thuraisamy","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs Institute for Cell Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Redding\u2010Ochoa","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Pletnikova","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Pathology and Anatomical Sciences Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Troncoso","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Center for Biomarker Discovery and Translation Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana S.","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-0893","authenticated-orcid":false,"given":"Ted M.","family":"Dawson","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs Institute for Cell Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Solomon H. 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