内质网应激——凋亡途径与创伤后应激障碍

Endoplasmic Reticulum Stress-apoptosis Pathways And Post-traumatic Stress Disorder

内质网(Endoplasmic Reticulum,ER)作为一种合成蛋白质的重要细胞器,对维持细胞稳态起重要作用。在内质网应激初期为了保证内质网功能的正常运行,启动未折叠蛋白反应来维持体内细胞存活,但当未折叠或错误折叠蛋白过多,则会诱导细胞凋亡。越来越多证据表明,由内质网应激介导的细胞凋亡路径对创伤后应激障碍的各个病理阶段都起着至关重要的作用。而氧化应激、钙稳态失衡和炎症反应作为导致内质网功能障碍的主要病理因素,也广泛参与创伤后应激障碍的发病。内质网应激启动非折叠蛋白反应,并通过活化内质网三条通路PERK、IRE1及ATF6,启动细胞凋亡路径。通过调控内质网应激-凋亡途径或抑制相关通路关键蛋白的表达以降低神经细胞凋亡率,可能会为创伤后应激障碍的治疗提供新的治疗靶点。而内质网应激-凋亡途径在创伤后应激障碍中的具体作用机制还有待进一步探究,该途径将有助于开发新的治疗创伤后应激障碍的药物和治疗策略。

The endoplasmic reticulum(ER),as an important organelle for protein synthesis,plays an important role in maintaining cellular homeostasis.In order to ensure the normal operation of endoplasmic reticulum function at the beginning of endoplasmic reticulum stress,an unfolded protein reaction is initiated to maintain cell survival in vivo,but when there are too many unfolded or misfolded proteins,apoptosis will be induced.There is growing evidence that endoplasmic reticulum stress-mediated apoptosis pathways play a critical role in all pathological stages of PTSD.Oxidative stress,calcium homeostasis imbalance and inflammatory response,as the main pathological factors leading to endoplasmic reticulum dysfunction,are also widely involved in the pathogenesis of post-traumatic stress disorder.Endoplasmic reticulum stress initiates the non-folding protein reaction and initiates the apoptosis pathway by activating the three endoplasmic reticulum pathways PERK,IRE1 and ATF6.Reducing the apoptosis rate of nerve cells by regulating the endoplasmic reticulum stress-apoptosis pathway or inhibiting the expression of key proteins of related pathways may provide new therapeutic targets for the treatment of post-traumatic stress disorder.The specific mechanism of endoplasmic reticulum stress-apoptosis pathway in PTSD needs to be further explored,and this pathway will help to develop new drugs and treatment strategies for PTSD.