Mercer, Audrey;
Jaunmuktane, Zane;
Hristova, Mariya;
Lange, Sigrun;
(2022)
Differential, Stage Dependent Detection of Peptidylarginine Deiminases and Protein Deimination in Lewy Body Diseases—Findings from a Pilot Study.
International Journal of Molecular Sciences
, 23
(21)
, Article 13117. 10.3390/ijms232113117.
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Abstract
Over 10 million people worldwide live with Parkinson’s 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—which 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.
| Type: | Article |
|---|---|
| Title: | Differential, Stage Dependent Detection of Peptidylarginine Deiminases and Protein Deimination in Lewy Body Diseases—Findings from a Pilot Study |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/ijms232113117 |
| Publisher version: | https://doi.org/10.3390/ijms232113117 |
| Language: | English |
| Additional information: | Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/license s/by/4.0/). |
| Keywords: | peptidylarginine deiminase; deimination/citrullination; post-translational modification; histone H3; neurodegeneration; Parkinson’s disease; Lewy body disease; brain |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10158285 |
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