结论:铁凋亡,一种以大量脂质过氧化介导的膜损伤为特征的调节性细胞死亡形式,加入了多系统疾病的进化。例如,神经退行性疾病,慢性阻塞性肺疾病和急性呼吸窘迫综合征,骨质疏松症和骨关节炎,等等。自从被确定为生物体中的第三个气体发射器以来,硫化氢(H2S)在铁中毒中的复杂作用已成为研究的前沿。
背景:在相关代谢途径中发现了新的靶标,包括转铁蛋白受体1,胱氨酸/谷氨酸反转运蛋白,和其他人,再加上新信号通路的探索,特别是p53信号通路和一氧化氮/核因子红细胞2相关因子2信号通路,等等。许多疾病如肺气肿和气道炎症,心肌疾病,老化动脉的内皮功能障碍,最近发现,通过H2S抑制铁中毒可以直接减轻创伤性脑损伤。安全,有效,并且已经开发了可耐受的新型H2S供体,并在I期临床试验中显示出了有希望的结果。
结果:铁性凋亡信号通路和致癌因子之间的复杂串扰导致抑制铁性凋亡时癌症的风险。值得注意的是,定向输送H2S仍然是一项具有挑战性的任务。
结论:发现更可靠和稳定的新型H2S供体并实现其靶向递送将使与H2S抑制铁死亡相关疾病的进一步临床试验成为可能,确定他们的安全,功效,和宽容。
Significance: Ferroptosis, a form of regulated cell death characterized by a large amount of lipid peroxidation-mediated membrane damage, joins the evolution of multisystem diseases, for instance, neurodegenerative diseases, chronic obstructive pulmonary disease, acute respiratory distress syndrome, osteoporosis, osteoarthritis, and so forth. Since being identified as the third gasotransmitter in living organisms, the intricate role of hydrogen sulfide (H2S) in ferroptosis has emerged at the forefront of research. Recent Advances: Novel targets in the relevant metabolic pathways have been found, including transferrin receptor 1, cystine/glutamate antiporter, and others, coupled with the exploration of new signaling pathways, particularly the p53 signaling pathway, the nitric oxide/nuclear factor erythroid 2-related factor 2 signaling pathway, and so on. Many diseases such as emphysema and airway inflammation, myocardial diseases, endothelial dysfunction in aging arteries, and traumatic brain injury have recently been found to be alleviated directly by H2S inhibition of ferroptosis. Safe, effective, and tolerable novel H2S donors have been developed and have shown promising results in phase I clinical trials. Critical Issues: Complicated cross talk between the ferroptosis signaling pathway and oncogenic factors results in the risk of cancer when inhibiting ferroptosis. Notably, targeted delivery of H2S is still a challenging task. Future Directions: Discovering more reliable and stable novel H2S donors and achieving their targeted delivery will enable further clinical trials for diseases associated with ferroptosis inhibition by H2S, determining their safety, efficacy, and tolerance.