In contrast to existing studies, our study is the first to shows that Hsp22 targets the NLRP3/caspase-1/IL-1β pathway to improve LPS-induced cognitive impairment, that Hsp22 preconditioning reduces the LPS-induced inflammatory response and cell apoptosis and improves learning and memory impairment in mice. Here, HSPB8 is linked to Cognitive impairment.