Ferroptosis promotes T-cell activation-induced neurodegeneration in multiple sclerosis.
Cell Mol Immunol
; 19(8): 913-924, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35676325
ABSTRACT
While many drugs are effective at reducing the relapse frequency of multiple sclerosis (MS), there is an unmet need for treatments that slow neurodegeneration resulting from secondary disease progression. The mechanism of neurodegeneration in MS has not yet been established. Here, we discovered a potential pathogenetic role of ferroptosis, an iron-dependent regulated cell death mechanism, in MS. We found that critical ferroptosis proteins (acyl-CoA synthetase long-chain family member 4, ACSL4) were altered in an existing genomic database of MS patients, and biochemical features of ferroptosis, including lipid reactive oxygen species (ROS) accumulation and mitochondrial shrinkage, were observed in the experimental autoimmune encephalitis (EAE) mouse model. Targeting ferroptosis with ferroptosis inhibitors or reducing ACSL4 expression improved the behavioral phenotypes of EAE mice, reduced neuroinflammation, and prevented neuronal death. We found that ferroptosis was an early event in EAE, which may promote T-cell activation through T-cell receptor (TCR) signaling in vitro and in vivo. These data indicate that ferroptosis may be a potential target for treating MS.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Ferroptose
/
Esclerose Múltipla
Limite:
Animals
Idioma:
En
Revista:
Cell Mol Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China