Kainic acid Induces production and aggregation of amyloid β-protein and memory deficits by activating inflammasomes in NLRP3- and NF-κB-stimulated pathways

• DOI: 10.18632/aging.102017
• Publication Date: 2019-06-10T17:57:52Z
• Authors: Yang Ruan; Xiang Qiu; Yu-Dan Lv; Dong Dong; Xiu-Juan Wu; Jie Zhu; Xiang-Yu Zheng
• Keywords: Pyrin domain

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 AD. However, underlying mechanism by inflammasomes influence AD remains unknown. The present study investigated damaging effect KA on neurons focusing inflammasome-mediated signaling pathways. Assessments using cultured microglia mouse brains demonstrated that specifically induced inflammasome activation. Mechanistic evaluations showed activated two major components inflammasomes, nucleotide binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) nuclear factor (NF)-κB, resulted in interleukin-1β (IL-1β) brain-derived neurotrophic (BDNF). Inhibition NLRP3 or NF-κB Bay11-7082 caused reduction KA-induced expression interleukin (IL)-1β BDNF. Moreover, knockdown receptors (KARs) Grik1 Grik3 suppression NF-κB, suggesting KARs function upstream mediate effects regulation IL-1β BDNF expression. Notably, was shown exert positive BACE1, blocked Bay11-7082. Overall, our results revealed acts against (Aβ) deposition, defects via further highlighted protective role defects.