Pyroptosis-mediator GSDMD promotes Parkinson's disease pathology via microglial activation and dopaminergic neuronal death.
Brain Behav Immun
; 119: 129-145, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38552923
ABSTRACT
GSDMD-mediated pyroptosis occurs in the nigrostriatal pathway in Parkinson's disease animals, yet the role of GSDMD in neuroinflammation and death of dopaminergic neurons in Parkinson's disease remains elusive. Here, our in vivo and in vitro studies demonstrated that GSDMD, as a pyroptosis executor, contributed to glial reaction and death of dopaminergic neurons across different Parkinson's disease models. The ablation of the Gsdmd attenuated Parkinson's disease damage by reducing dopaminergic neuronal death, microglial activation, and detrimental transformation. Disulfiram, an inhibitor blocking GSDMD pore formation, efficiently curtailed pyroptosis, thereby lessening the pathology of Parkinson's disease. Additionally, a modification in GSDMD was identified in the blood of Parkinson's disease patients in contrast to healthy subjects. Therefore, the detected alteration in GSDMD within the blood of Parkinson's disease patients and the protective impact of disulfiram could be promising for the diagnostic and therapeutic approaches against Parkinson's disease.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Microglia
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Proteínas de Ligação a Fosfato
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Dissulfiram
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Neurônios Dopaminérgicos
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Piroptose
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Brain Behav Immun
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Brain behav. immun
/
Brain, behavior, and immunity
Assunto da revista:
ALERGIA E IMUNOLOGIA
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CEREBRO
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PSICOFISIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China