Abstract
Stroke imposes significant global socio-economic burdens, yet the absence of clinically approved anti-ischemic drugs and limited thrombolysis availability underscore the critical need for novel therapeutic target. To identify novel anti-ischemic therapeutic targets, we conducted a comprehensive proteomics analysis subsequent to in vitro ischemia/reperfusion of epithelial cells highly sensitive to oxygen deprivation with and without eIF5A inhibition, a strategy recently acknowledged for its efficacy in alleviating ischemic-anoxic damage. We identified seryl-tRNA synthetase (serRS) as a promising target through several key findings. Initially, we validated its inhibition as highly efficient in reducing cell death in an in vitro model of ischemia/reperfusion. Subsequently, we demonstrated that inhibition of serRS substantially decreased infarct volume and alleviated both motor and cognitive deficits in a murine model of transient focal cerebral ischemia, underscoring the in vivo therapeutic potential of targeting serRS. Overall, this Proof-of-Concept study unveils serRS as a novel anti-ischemic target, laying groundwork for the discovery and development of new inhibitors with therapeutic promise against ischemic-related diseases.
Get full access to this article
View all access options for this article.
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
