TRIM62 knockdown by inhibiting the TLR4/NF-κB pathway and NLRP3 inflammasome attenuates cognitive impairment induced by diabetes in mice

抄録

The tripartite motif 62 is an E3 ubiquitin ligase protein that regulates cellular processes, including differentiation, immunity, development and apoptosis, leading to various disease states, such as cancer and inflammatory diseases. However, the role and mechanism of the tripartite motif 62 in the process of diabetic-induced cognitive impairment have not been reported. Therefore, the aim of this study was to investigate the role and mechanism of the tripartite motif 62 in diabetic-induced cognitive impair­ment. The results showed that the expression of the tripartite motif 62 was up-regulated in diabetic mice. Silencing of TRIM62 increased body weight and decreased fasting blood glucose in diabetic mice. In addition, knockdown of the tripartite motif 62 inhibited STZ-induced inflammation, apoptosis and oxidative stress. Further studies showed that the TLR4/NF-κB pathway and NLRP3 inflammasomes were involved in the regulation of diabetic mice by the tripartite motif 62. More importantly, inhibition of the tripartite motif 62 improved cognitive impairment and learning ability in mice. In conclusion, inhibition of TRIM62 inhibits STZ-induced inflammation, cell apoptosis and oxidative stress, and improves the cognitive ability of mice. Therefore, the tripartite motif 62 may be an important target for the treatment of diabetes-induced cognitive impairment.