The Sirtuin 5 Inhibitor MC3482 Ameliorates Microgliainduced Neuroinflammation Following Ischaemic Stroke by Upregulating the Succinylation Level of Annexin-A1.
J Neuroimmune Pharmacol
; 19(1): 17, 2024 May 08.
Article
em En
| MEDLINE
| ID: mdl-38717643
ABSTRACT
In our previous study, we concluded that sirtuin 5 (SIRT5) was highly expressed in microglia following ischaemic stroke, which induced excessive neuroinflammation and neuronal injury. Therefore, SIRT5-targeting interventions should reduce neuroinflammation and protect against ischaemic brain injury. Here, we showed that treatment with a specific SIRT5 inhibitor, MC3482, alleviated microglia-induced neuroinflammation and improved long-term neurological function in a mouse model of stroke. The mice were administrated with either vehicle or 2 mg/kg MC3482 daily for 7 days via lateral ventricular injection following the onset of middle cerebral artery occlusion. The outcome was assessed by a panel of tests, including a neurological outcome score, declarative memory, sensorimotor tests, anxiety-like behavior and a series of inflammatory factors. We observed a significant reduction of infarct size and inflammatory factors, and the improvement of long-term neurological function in the early stages during ischaemic stroke when the mice were treated with MC3482. Mechanistically, the administration of MC3482 suppressed the desuccinylation of annexin-A1, thereby promoting its membrane recruitment and extracellular secretion, which in turn alleviated neuroinflammation during ischaemic stroke. Based on our findings, MC3482 offers promise as an anti-ischaemic stroke treatment that targets directly the disease's underlying factors.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Anexina A1
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Microglia
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Sirtuínas
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AVC Isquêmico
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Doenças Neuroinflamatórias
Limite:
Animals
Idioma:
En
Revista:
J Neuroimmune Pharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
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FARMACOLOGIA
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NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China