Kainic acid (KA) treatment causes neuronal degeneration, which is a feature of Alzheimer’s disease (AD) symptoms such as amyloid β-protein production and memory deficits. Inflammasomes are known to be critical for the progression of AD. However, the underlying mechanism by which inflammasomes influence AD progression remains unknown. The present study investigated the damaging effect of KA on neurons by focusing on the inflammasome-mediated signaling pathways. Assessments using cultured microglia and mouse brains demonstrated that KA treatment specifically induced inflammasome activation. Mechanistic evaluations showed that KA activated two major components of inflammasomes, nucleotide binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) and nuclear factor (NF)-κB, which resulted in the production of interleukin-1β (IL-1β) and brain-derived neurotrophic factor (BDNF). Inhibition of NLRP3 or NF-κB by Bay11-7082 caused a reduction in the KA-induced expression of interleukin (IL)-1β and BDNF. Moreover, knockdown of the expression of KA receptors (KARs) such as Grik1 and Grik3 induced suppression of NLRP3 and NF-κB, suggesting that KARs function upstream of NLRP3 and NF-κB to mediate the effects of KA on regulation of IL-1β and BDNF expression. Notably, IL-1β was shown to exert positive effects on the expression of BACE1, which is blocked by Bay11-7082. Overall, our results revealed that Bay11-7082 acts against KA-induced neuronal degeneration, amyloid β-protein (Aβ) deposition, and memory defects via inflammasomes and further highlighted the protective role of Bay11-7082 in KA-induced neuronal defects.