Mitochondrial complex I activity in microglia sustains neuroinflammation.
Nature
; 628(8006): 195-203, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38480879
ABSTRACT
Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Microglia
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Complexo I de Transporte de Elétrons
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Doenças Neuroinflamatórias
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Inflamação
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Nature
Ano de publicação:
2024
Tipo de documento:
Article