Abstract

SUN, Fengqin  and  HUANG, Wei. 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. Invest. clín [online]. 2025, vol.66, n.2, pp.191-204.  Epub June 25, 2025. ISSN 0535-5133.  https://doi.org/10.54817/ic.v66n2a06.

Inflammation-induced neuronal death is the primary cause of Alzheimer’s disease (AD). p300 plays an important role in brain disorders. However, the role of p300 in AD remains unclear. This study aimed to investigate the potential of p300 in an in vitro model of AD. Protein expression was detected using western blotting. The mRNA levels were determined by reverse transcription-quantitative polymerase chain reaction. Cytokine release was detected using an enzyme-linked immunosorbent assay. Cellular function was determined using the cell counting kit-8, lactate dehydrogenase, and flow cytometry assays. Chromatin immunoprecipitation and luciferase assays verified the interaction between nuclear factor kappa B (NF-κB) and the NLR family pyrin domain containing 3 (NLRP3). E1A binding protein p300 (p300) was overexpressed in the Aβ1-42 induced AD model in vitro. However, treatment with the p300 inhibitor (GNE-049) alleviated inflammation and Aβ1-42-induced pyroptosis in the neurons. p300 activates NF-κB, which antagonizes the effects of GNE-049 and promotes neuronal pyroptosis. Moreover, NF-κB epigenetically activates the NLRP3 inflammasome. The p300/NF-κB pathway promotes neuronal pyroptosis in an in vitro AD model by activating the NLRP3 inflammasome. Therefore, the p300/NF-κB/NLRP3 signalling pathway may be a potential therapeutic target for AD.

Keywords : Alzheimer’s disease; p300; pyroptosis; NLRP3 inflammasome.

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