The p300-NF-κB pathway induces the activation of the NLRP3 inflammasome and the pyroptosis of neurons in an in vitro model of Alzheimer’s disease.

En el modelo in vitro de la enfermedad de Alzheimer, la vía p300 NF - Kappa B induce la activación del inflamasoma NLRP3 y la piroptosis neuronal en un modelo in vitro de la enfermedad de Alzheimer.

• Fengqin Sun Neurology Department, The Third People’s Hospital of Yunnan Province, China. https://orcid.org/0009-0009-0865-8011
• Wei Huang Neurology Department, The Third People’s Hospital of Yunnan Province, China. https://orcid.org/0009-0008-9840-1633

DOI: https://doi.org/10.54817/IC.v66n2a06

Palabras clave: enfermedad de Alzheimer, P300, muerte por quemadura celular, cuerpo inflamatorio nlrp3

Resumen

La muerte neuronal inducida por la inflamación es la principal causa de la enfermedad de Alzheimer (AD). El p300 juega un papel importante en las enfermedades cerebrales. Sin embargo, se desconoce el papel del p300 en la AD. El objetivo de este estudio es explorar el potencial del p300 en modelos in vitro de AD. Se utilizó Western blot para detectar la expresión de proteínas. Los niveles de ARNm se determinaron mediante la reacción cuanti- tativa en cadena de la polimerasa de transcripción inversa. Se utilizó la prueba de inmunoabsorción enzimática para detectar la liberación de citocinas. La función celular se determinó mediante el contador celular Kit - 8, la lactato deshidrogenasa y la medición con citometría de flujo. La interacción entre el factor nuclear Kappa b (nf - Kappa b) y el dominio Pirin 3 (nlrp3), que contiene la familia NLR, fue verificada por inmunoprecipitación de cromatina y detec- ción de luciferasa. La proteína de unión a E1A p300 (p300) está sobreexpresada en un modelo de AD inducido por Aβ _1-42. Sin embargo, el tratamiento con un inhibidor del p300 (GNE - 049) redujo la inflamación y redujo la muerte por piroptosis neuronal inducida por Aβ _1-42 . El p300 activa NF - Kappa b, que inhibe el efecto del GNE - 049 y promueve la muerte por piroptosis neuronal. Además, NF-κB epigeneticamentelly activa el NLRP3 inflamasoma Epigenética NF-Kappa B activa los cuerpos inflamatorios nlrp3. La vía p300 / NF - Kappa B promueve la muerte focal neuronal en modelos in vitro de AD activando el inflamasoma NLRP3. Por lo tanto, la transmisión de la señal p300/NF-Kappa B/NLRP3 puede ser un objetivo terapéutico potencial para la AD.

Citas

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