Polo-like kinase 2 promotes microglial activation via regulation of the HSP90α/IKKβ pathway

• DOI: 10.1016/j.celrep.2024.114827
• Publication Date: 2024-10-09T10:36:04Z
• Authors: Junjie Cheng; Lei Wu; Xiaowan Chen; Shuai Li; Zhirou Xu; Renjuan Sun; Yiwei Huang; Peng Wang; Jiawei Ouyang; Panpan Pei; Huicui Yang; Guanghui Wang; Xuechu Zhen; Long-Tai Zheng
• Keywords: IκB kinase

Highlights•LPS rapidly induces PLK2 expression in microglial cells•Inhibition of suppresses LPS-induced activation via NF-κB signaling•PLK2 activates signaling through phosphorylating HSP90α•Knockout microglia ameliorated neuroinflammation and dopaminergic neuron lossSummaryPolo-like kinase 2 (PLK2) is a serine/threonine protein associated with the regulation synaptic plasticity centriole duplication. We identify as crucial early-response gene lipopolysaccharide (LPS)-stimulated cells. Knockdown or inhibition remarkably attenuates proinflammatory factors cells by suppressing inhibitor nuclear factor kappa B subunit beta (IKKβ)-nuclear (NF)-κB pathway. heat shock 90 alpha (HSP90α), regulator IKKβ activity, novel substrate. pharmacological HSP90α abolishes PLK2-mediated transcriptional activity inflammatory activation. Furthermore, phosphoproteomic analysis pinpoints Ser252 Ser263 on phosphorylation targets PLK2. Lastly, conditional knockout dramatically ameliorates subsequent loss an intracranial mouse Parkinson's disease (PD) model. The present study reveals that promotes IKKβ-NF-κB pathway.Graphical abstract