Molecular regulatory mechanism of the SIRT2/NF-κB p65 signaling pathway in ferroptosis-promoted spinal cord injury repair.

backgroundSpinal cord injury (SCI) is a debilitating neurological condition that often results in long-term disability and functional impairment. Recent studies have identified ferroptosis as a significant pathological mechanism in SCI. SIRT2, a deacetylase enzyme, is closely associated with inflammatory responses and apoptosis, playing a crucial role in the pathogenesis of various neurological disorders. This research aims to elucidate the specific mechanisms by which SIRT2 overexpression inhibits ferroptosis and promotes SCI repair through the deacetylation of nuclear factor-κB (NF-κB) p65.

resultsUtilizing cell models and a rat SCI model, we discovered that SIRT2 overexpression promotes NF-κB p65 deacetylation, subsequently inhibiting ferroptosis and oxidative stress. Conversely, the use of AK-7 elevated NF-κB p65 acetylation levels, exacerbating ferroptosis and oxidative stress. In SCI rats, intrathecal injection of SIRT2-overexpressing recombinant adenovirus successfully inhibited NF-κB p65 acetylation and ferroptosis in the dorsal root ganglia, thereby reducing neuronal apoptosis and enhancing motor function recovery.

conclusionIn summary, these findings indicate that SIRT2 overexpression can suppress ferroptosis through NF-κB p65 deacetylation, facilitating SCI repair. Therefore, a deeper understanding of the interaction between SIRT2 and NF-κB p65 and their roles in the regulation of ferroptosis is of paramount importance for developing novel therapeutic approaches for spinal cord injury.