PAD2 dysregulation and aberrant protein citrullination feature prominently in reactive astrogliosis and myelin protein aggregation in sporadic ALS.
Neurobiol Dis
; 192: 106414, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38253209
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Citrullination
/
Amyotrophic Lateral Sclerosis
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Neurobiol Dis
Journal subject:
NEUROLOGIA
Year:
2024
Type:
Article
Affiliation country:
United States