Overexpression of NAF-1 ameliorates Ischemic Stroke in rats by inhibiting PINK1/Parkin-mediated mitophagy

Abstract

Ischemic stroke (IS) has a high mortality and disability rate worldwide. NAF-1 is involved in the occurrence and development of nervous system diseases, but its involvement in the pathophysiology of IS is unclear. In this study, we investigated the role of NAF-1 in IS. Middle cerebral artery occlusion and reperfusion in Sprague-Dawley rats was used as an in vivo model of IS. Moreover, oxygen-glucose deprivation and reoxygenation of PC12 cells was used for in vitro study. Intracellular NAF-1 protein expression was influenced by LV-NAF-1 or siRNA. Quantitative real-time PCR and western blot analysis showed that NAF-1 was significantly downregulated following IS. Overexpression of NAF-1 reduced mitophagy in PC12 cells, and it alleviated tissue damage in vivo in rats and cell injury in vitro. In contrast, knockdown of NAF-1 increased mitophagy and worsened cell damage. These findings suggest that NAF-1 may have potential as a therapeutic target for IS.

CDGSH iron-sulfur domain 2 as a therapeutic target for stroke: an opinion article

“…Strategies to enhance CISD2, such as overexpression, cryogen spray cooling, and application of the phytochemical curcumin or wild bitter melon, can be beneficial for neurological injury or disease (Kung, 2021b ). In stroke, CISD2-overexpression greatly ameliorated ischemia-associated mitochondrial dysfunction and subsequent apoptosis (Fan et al, 2022 ; Ren et al, 2022 ; Hu et al, 2023 ).…”