{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T20:54:14Z","timestamp":1780692854490,"version":"3.54.1"},"reference-count":57,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"internal University of Westminster funding"},{"name":"UCL School of Pharmacy internal funding"},{"name":"Department of Health\u2019s NIHR Biomedical Research Centre\u2019s funding scheme"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Over 10 million people worldwide live with Parkinson\u2019s disease (PD) and 4% of affected people are diagnosed before the age of 50. Research on early PD-related pathways is therefore of considerable importance. Peptidylarginine deiminases (PADs) are a family of calcium-activated enzymes that, through post-translational deimination of arginine to citrulline, contribute to changes in protein function, including in pathological processes. Recent studies have highlighted roles for PADs in a range of neurological disorders including PD, but overall, investigations on PADs in Lewy body disease (LBD), including PD, are still scarce. Hence, the current pilot study aimed at performing an immunohistochemistry screen of post-mortem human brain sections from Braak stages 4-6 from PD patients, as well as patients with incidental LBD (ILBD). We assessed differences in PAD isozyme detection (assessing all five PADs), in total protein deimination\/citrullination and histone H3 deimination\u2014which is an indicator of epigenetic changes and extracellular trap formation (ETosis), which can elicit immune responses and has involvement in pathogenic conditions. The findings of our pilot study indicate that PADs and deimination are increased in cingulate cortex and hippocampus, particularly in earlier stages of the disease. PAD2 and PAD3 were the most strongly upregulated PAD isozymes, with some elevation also observed for PAD1, while PAD4 and PAD6 increase was less marked in PD brains. Total protein deimination and histone H3 deimination were furthermore increased in PD brains, with a considerable increase at earlier Braak stages, compared with controls. Our findings point to a significant contribution of PADs, which may further aid early disease biomarker discovery, in PD and other LBDs.<\/jats:p>","DOI":"10.3390\/ijms232113117","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T07:26:50Z","timestamp":1667114810000},"page":"13117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential, Stage Dependent Detection of Peptidylarginine Deiminases and Protein Deimination in Lewy Body Diseases\u2014Findings from a Pilot Study"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5086-2560","authenticated-orcid":false,"given":"Audrey","family":"Mercer","sequence":"first","affiliation":[{"name":"Department of Pharmacology, UCL School of Pharmacy, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zane","family":"Jaunmuktane","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Hristova","sequence":"additional","affiliation":[{"name":"Perinatal Brain Repair Group, Department of Neonatology, UCL Institute for Women\u2019s Health, London WC1E 6HU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7193-3102","authenticated-orcid":false,"given":"Sigrun","family":"Lange","sequence":"additional","affiliation":[{"name":"Tissue Architecture and Regeneration Research Group, School of Life Sciences, University of Westminster, London W1W 6XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. 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