1. PAD2 dysregulation and aberrant protein citrullination feature prominently in reactive astrogliosis and myelin protein aggregation in sporadic ALS.
- Author
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Yusuf IO, Parsi S, Ostrow LW, Brown RH, Thompson PR, and Xu Z
- Subjects
- Animals, Humans, Mice, Gliosis metabolism, Hydrolases genetics, Hydrolases metabolism, Myelin Proteins metabolism, Myelin Sheath pathology, Protein Aggregates, Protein-Arginine Deiminase Type 2 metabolism, Protein-Arginine Deiminases metabolism, Proteins metabolism, Spinal Cord pathology, Amyotrophic Lateral Sclerosis metabolism, Citrullination
- Abstract
Alteration in protein citrullination (PC), a common posttranslational modification (PTM), contributes to pathogenesis in various inflammatory disorders. We previously reported that PC and protein arginine deiminase 2 (PAD2), the predominant enzyme isoform that catalyzes this PTM in the central nervous system (CNS), are altered in mouse models of amyotrophic lateral sclerosis (ALS). We now demonstrate that PAD2 expression and PC are altered in human postmortem ALS spinal cord and motor cortex compared to controls, increasing in astrocytes while trending lower in neurons. Furthermore, PC is enriched in protein aggregates that contain the myelin proteins PLP and MBP in ALS. These results confirm our findings in ALS mouse models and suggest that altered PAD2 and PC contribute to neurodegeneration in ALS., Competing Interests: Declaration of competing interest PRT holds equity in Padlock Therapeutics a subsidiary of Bristol Myers Squibb. The other authors have no competing interests to declare that are relevant to this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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