DCC/netrin-1 regulates cell death in oligodendrocytes after brain injury.
Cell Death Differ
; 30(2): 397-406, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36456775
ABSTRACT
Hallmark pathological features of brain trauma are axonal degeneration and demyelination because myelin-producing oligodendrocytes (OLs) are particularly vulnerable to injury-induced death signals. To reveal mechanisms responsible for this OL loss, we examined a novel class of "death receptors" called dependence receptors (DepRs). DepRs initiate pro-death signals in the absence of their respective ligand(s), yet little is known about their role after injury. Here, we investigated whether the deleted in colorectal cancer (DCC) DepR contributes to OL loss after brain injury. We found that administration of its netrin-1 ligand is sufficient to block OL cell death. We also show that upon acute injury, DCC is upregulated while netrin-1 is downregulated in perilesional tissues. Moreover, after genetically silencing pro-death activity using DCCD1290N mutant mice, we observed greater OL survival, greater myelin integrity, and improved motor function. Our findings uncover a novel role for the netrin-1/DCC pathway in regulating OL loss in the traumatically injured brain.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
/
Proteínas Supressoras de Tumor
/
Netrina-1
/
Receptor DCC
Limite:
Animals
Idioma:
En
Revista:
Cell Death Differ
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos