%0 Journal Article
%T Therapeutic effects of exendin-4 on spinal cord injury via restoring autophagy function and decreasing necroptosis in neuron.
%A Gao X
%A Li QP
%A Hao JR
%A Sun K
%A Feng H
%A Guo KJ
%A Gao C
%J CNS Neurosci Ther
%V 30
%N 7
%D 2024 Jul
%M 39004783
%F 7.035
%R 10.1111/cns.14835
%X <B>OBJECTIVE: </B>Necroptosis is one of programmed death that may aggravate spinal cord injury (SCI). We aimed to investigate the effect and mechanism of exendin-4 (EX-4) on the recovery of motor function and necroptosis after SCI.<BR><B>METHODS: </B>The SD rats with left hemisection in the T10 spinal cord as SCI model were used. The behavior tests were measured within 4 weeks. The effects of EX-4 on necroptosis-associated proteins and autophagy flux were explored. In addition, the SHSY5Y cell model was introduced to explore the direct effect of EX-4 on neurons. The effect of lysosome was explored using mTOR activator and AO staining.<BR><B>RESULTS: </B>EX-4 could improve motor function and limb strength, promote the recovery of autophagy flux, and accelerate the degradation of necroptosis-related protein at 3 d after injury in rats. EX-4 reduced lysosome membrane permeability, promoted the recovery of lysosome function and autophagy flux, and accelerated the degradation of necroptosis-related proteins by inhibiting the phosphorylation level of mTOR in the SHSY5Y cell model.<BR><B>CONCLUSIONS: </B>Our results demonstrated that EX-4 may improve motor function after SCI via inhibiting mTOR phosphorylation level and accelerating the degradation of necroptosis-related proteins in neurons. Our findings may provide new therapeutic targets for clinical treatment after SCI.