SENP1 regulates intermittent hypoxia-induced microglia mediated inflammation and cognitive dysfunction via wnt/β-catenin pathway.

Obstructive sleep apnea syndrome (OSAS), characterized by repeated narrow or collapse of the upper airway during sleep, resulting in periodic reductions or cessations in ventilation, consequent hypoxia, hypercapnia, increased sympathetic activity and sleep fragmentation, places a serious burden on society and health care. Intermittent hypoxia (IH), which cause central nervous system (CNS) inflammation, and ultimately lead to neuropathy, is thought to be a crucial contributor to cognitive impairment in OSAS. Wnt signaling pathway exerts an important role in the regulation of CNS disorders. Particularly, it may be involved in the regulation of neuroinflammation and cognitive dysfunction. However, its underlying mechanism remains poorly understood. Accumulating evidence demonstrated that Wnt signaling pathway may inhibited in a variety of neurological disorders. Recently studies revealed that SUMOylation was participated in the regulation of neuroinflammation. Members of Wnt/β-catenin pathway may be targets of SUMOylation. In vitro and in vivo molecular biology experiments explored the regulatory mechanism of SUMOylation on Wnt/β-catenin in IH-induced neuroinflammation and neuronal injury, which demonstrated that IH induced the SUMOylation of β-catenin, microglia mediated inflammation and neuronal damage. Moreover, SENP1 regulated the de-SUMOylation of β-catenin, triggered Wnt/β-catenin pathway, and alleviated neuroinflammation and neuronal injury, thus improving IH-related mice cognitive dysfunction.