Dual regulation of Atf3 and Lonp1 as therapeutic targets in cerebral ischaemia-reperfusion injury

Abstract

Background Cerebral ischemia-reperfusion injury (CIRI) leads to cognitive dysfunction, neuronal death, and inflammation. Understanding the molecular mechanisms underlying CIRI is crucial for developing effective therapeutic strategies.Objective This study aims to investigate the roles of activating transcription factor 3 (Atf3) and lon protease homolog 1 (Lonp1) in CIRI, particularly focusing on how Atf3 regulates Lonp1 expression and its effects on mitochondrial function.Methods Single-cell transcriptomics and proteomic analyses were employed to explore Atf3's influence on Lonp1 and its subsequent impact on neuronal survival and apoptosis.Results The findings indicate that Atf3 plays a crucial role in modulating Lonp1 expression, which in turn affects mitochondrial function, neuronal survival, and apoptotic pathways.Conclusion This study provides new insights into the regulatory mechanisms of Atf3 and Lonp1 in CIRI, identifying potential therapeutic targets for managing ischemic brain injury and neurodegenerative diseases.