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The Extracellular Vesicle Citrullinome and Signature in a Piglet Model of Neonatal Seizures

Mitra, Subhabrata; Harvey-Jones, Kelly; Kraev, Igor; Verma, Vinita; Meehan, Christopher; Mintoft, Alison; Norris, Georgina; ... Lange, Sigrun; + view all (2023) The Extracellular Vesicle Citrullinome and Signature in a Piglet Model of Neonatal Seizures. International Journal of Molecular Sciences , 24 (14) , Article 11529. 10.3390/ijms241411529. Green open access

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Abstract

Neonatal seizures are commonly associated with acute perinatal brain injury, while understanding regarding the downstream molecular pathways related to seizures remains unclear. Furthermore, effective treatment and reliable biomarkers are still lacking. Post-translational modifications can contribute to changes in protein function, and post-translational citrullination, which is caused by modification of arginine to citrulline via the calcium-mediated activation of the peptidylarginine deiminase (PAD) enzyme family, is being increasingly linked to neurological injury. Extracellular vesicles (EVs) are lipid-bilayer structures released from cells; they can be isolated from most body fluids and act as potential liquid biomarkers for disease conditions and response to treatment. As EVs carry a range of genetic and protein cargo that can be characteristic of pathological processes, the current study assessed modified citrullinated protein cargo in EVs isolated from plasma and CSF in a piglet neonatal seizure model, also following phenobarbitone treatment. Our findings provide novel insights into roles for PAD-mediated changes on EV signatures in neonatal seizures and highlight the potential of plasma- and CSF-EVs to monitor responses to treatment.

Type: Article
Title: The Extracellular Vesicle Citrullinome and Signature in a Piglet Model of Neonatal Seizures
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/ijms241411529
Publisher version: https://doi.org/10.3390/ijms241411529
Language: English
Additional information: © 2023 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/licenses/by/4.0/).
Keywords: neonatal; seizure; phenobarbitone; extracellular vesicles (EVs); citrullination/deimination; peptidylarginine deiminase (PAD); liquid biopsy; biomarker; KEGG
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Neonatology
URI: https://discovery.ucl.ac.uk/id/eprint/10173968
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