Academician Song Weihong's team reveals USP25 as an important regulatory molecule for ischemic stroke injury

Recently, the research team led by Academician Song Weihong, a member of the Canadian Academy of Health Sciences and director of the Oujiang Laboratory, and Academician Wang Xu, published a research paper titled "USP25 inhibits neuroinflammatory responses after cerebral ischemic stroke by deubiquitinating TAB2" in the internationally renowned journal "Advanced Science" (TOP 1 region of the Chinese Academy of Sciences, IF=15.1). They found that the deubiquitinase USP25 alleviates ischemic stroke damage by inhibiting microglia mediated neuropathy, and for the first time, USP25 inhibits inflammatory signal transduction by cleaving the K63 specific ubiquitination chain on TAB2. This study elucidates the role and molecular mechanism of USP25 in alleviating ischemic stroke injury, and identifies a novel intervention target for neuroprotective treatment of ischemic stroke.

Ischemic stroke is a life threatening cerebrovascular disease with a high incidence rate, disability rate and mortality, accounting for more than 80% of the total number of stroke cases. This study found that the deficiency of the deubiquitinase USP25 significantly exacerbated ischemic stroke injury in mice. Functionally, USP25 does not directly affect neuronal death caused by glucose deprivation, but rather reduces neuronal damage and functional deficits caused by ischemic stroke by inhibiting neuroinflammatory responses mediated by microglia.

缺血性腦卒中后，USP25敲除小鼠大腦中小膠質(zhì)細(xì)胞活化增加

This study found that compared with normal microglia, USP25 expression was upregulated in microglia in the ischemic penumbra of ischemic stroke patients and mice, suggesting that USP25 inhibits neuroinflammatory responses through stress-induced upregulation after ischemic stroke.

Upregulation of USP25 expression in microglia of ischemic penumbra in patients with ischemic stroke

In terms of molecular mechanism, this study found that USP25 can cleave the K63 specific polyubiquitin chain on TAB2, thereby reducing the activation of NF - κ B and MAPK signaling pathways. Silencing or overexpression of TAB2 in the mouse brain alleviated or exacerbated ischemic stroke injury, and both silencing and overexpression of USP25 eliminated the impact of USP25 deficiency on the disease. This study not only identified a novel target for the treatment of ischemic stroke, but also provided a new regulatory mechanism for inflammatory signal transduction.

Mechanism diagram of this study

This article is quoted from Oujiang Laboratory