Stabilization of HSP70 by deubiquitinase OTUB1 attenuates sleep deprivation-induced cognitive impairment in mice.

This study aims to investigate the role of the deubiquitinase OTUB1 in regulating sleep deprivation-induced cognitive impairment in mice and to elucidate the underlying molecular pathways. A mouse model of sleep deprivation was established, and mice were pretreated with OTUB1 protein. Cognitive function was assessed using the Y-maze test, the novel object recognition test (NORT), and the open field test. In vitro experiments involved the generation of OTUB1-overexpressing cell lines. Target gene expression was analyzed by western blot, qRT-PCR, and ELISA assays. Protein-protein interactions were assessed via co-immunoprecipitation. Our findings revealed a decrease in heat shock protein 70 (HSP70) protein levels in the hippocampus of sleep-deprived mice, along with an interaction between OTUB1 and HSP70 in mouse microglial cells. OTUB1 stabilized HSP70 by reducing its polyubiquitination. Furthermore, OTUB1 ameliorated sleep deprivation-induced cognitive deficits and reduced neuroinflammation in the hippocampus, as evidenced by changes in cytokine levels. OTUB1 mitigates sleep deprivation-induced cognitive impairment and neuroinflammation in the hippocampus by stabilizing HSP70 and attenuating inflammatory responses.