酸性鞘磷脂酶活性调控及相关药物研究进展

酸性鞘磷脂酶(ASM)是鞘磷脂代谢的关键酶,调节细胞增殖、分化、衰老和凋亡等。ASM过少或缺陷易引起尼曼-匹克病,过多会导致神经性病变、抑郁症、脓毒症和糖尿病等。研究发现,ASM的激活受环境因素、药物因素和其他因素的影响,细菌、病毒、电离辐射、重金属、心理压力、乙醇和细胞因子等可激活ASM,诱发上述疾病发生。应用ASM直接抑制或功能性抑制药物可减轻相关疾病带来的损伤。ASM活性增强,可促使肿瘤细胞凋亡,具有抗肿瘤作用,有望成为新的抗肿瘤药物靶标及肿瘤预测因子。本文就ASM活性调控及相关药物研究进展进行简要综述。

Research progress in regulation of acid sphingomyelinase activity and its related drugs

Acid sphingomyelinase(ASM)is a key enzyme in the metabolism of sphingomyelin,which regulates important transduction processes such as cell proliferation,differentiation,senescence and apoptosis.Too little or deficiency of ASM can cause Niemann-Pick disease,while excess ASM can lead to neurological diseases,depression,sepsis,diabetes and other diseases.Studies have found that the activation of ASM is affected by exogenous environmental factors,drug factors and other factors.Bacteria,viruses,ionizing radiation,heavy metals,psychological stress,alcohol and cytokines can activate ASM activity and induce the above diseases.The use of ASM direct inhibition or functional inhibition drugs can reduce the damage caused by related diseases.The enhanced activity of ASM can promote the apoptosis of tumor cells and anti-tumor effect,which is expected to be a new tumor drug target and tumor predictor.This article briefly reviews the regulation of ASM activity and related drug research.