Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder.
Neurosci Bull
; 40(8): 1104-1114, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38227181
ABSTRACT
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) accompanied by blood-brain barrier (BBB) disruption. Dysfunction in microglial lipid metabolism is believed to be closely associated with the neuropathology of NMOSD. However, there is limited evidence on the functional relevance of circulating lipids in CNS demyelination, cellular metabolism, and microglial function. Here, we found that serum low-density lipoprotein (LDL) was positively correlated with markers of neurological damage in NMOSD patients. In addition, we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB, directly activating microglia. This activation leads to excessive phagocytosis of myelin debris, inhibition of lipid metabolism, and increased glycolysis, ultimately exacerbating myelin damage. We also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in NMOSD. These findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage, highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neuromielite Óptica
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Microglia
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Lipoproteínas LDL
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neurosci Bull
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China