小胶质细胞活化在神经退行性疾病的发生、发展过程中起着重要作用。HSP90/IκB激酶（IKK）信号在小胶质细胞活化过程中起重要作用，但是其上游的调控机制尚不清楚。我们前期蛋白组学研究发现，HSP90α与丝/苏氨酸蛋白激酶Polo样激酶2(PLK2)相互作用；PLK2在活化的小胶质细胞中高表达，PLK2缺失可抑制小胶质细胞活化以及NF-κB激活；敲低或抑制HSP90α可阻断PLK2介导的NF-κB激活。因此，我们推测作为蛋白激酶PLK2可能通过磷酸化HSP90α促进小胶质细胞活化。本研究将运用分子细胞生物学、条件性PLK2敲除小鼠等手段探讨PLK2通过正性调控HSP90α/IKK促进小胶质细胞活化作用，阐明PLK2磷酸化HSP90α的分子机制及其在小胶质细胞活化中的作用。这一研究将为寻找调节神经炎症的途径以及控制神经退行性疾病的发生和发展提供新思路和潜在靶点。

Microglial activation plays an important role in the pathogenesis and progression of neurodegenerative diseases. The heat shock protein 90(HSP90)/IκB kinase (IKK) signaling plays a critical role in the microglial activation. However, its upstream mechanisms remain unclear. Recently, our immunoprecipitation coupled liquid chromatography tandem mass spectroscopy (LC-MS/MS) analysis found that HSP90α interacted with Polo-like kinase (PLK) 2, a serine/threonine-protein kinase. Knockdown of PLK2 significantly inhibited microglial activation and NF-κB activation. In addition, HSP90 inhibitor geldanamycin or knockdown of HSP90α suppressed PLK2 mediated NF-κB activation. Therefore, we hypothesize that as a protein kinase, PLK2 could promote microglial activation through phosphorylating HSP90α. To confirm this hypothesis, we will investigate the role of PLK2 in activation of HSP90/IKK signaling and subsequent microglial inflammatory activation. We will also investigate the role and molecular mechanisms of HSP90α phosphorylation on PLK2-mediated microglial activation. This study will provide new insight into the regulatory mechanisms of microglial inflammatory activation and will also provide a potential molecular target for developing new therapeutic interventions in neurodegenerative diseases.