Kongensin A抑制坏死性凋亡途径在慢性肾脏病中作用的研究进展

Research progress of the role of Kongensin A inhibiting necrotic apoptotic pathways in chronic kidney disease

坏死性凋亡(Necroptosis)在炎症性、免疫性和神经退行性等疾病的发病机制中起着重要作用,参与了慢性肾脏病(CKD)的发生发展,但其明确的分子机制还没有被完全阐明。热休克蛋白90 (HSP90)作为一种重要的分子伴侣,底物蛋白种类繁多,广泛参与诸多生命活动,在维持细胞内蛋白质稳态方面起到关键的调节作用。随着研究的深入,研究者发现坏死性凋亡途径中的核心组成部分受体相互作用蛋白1 (RIP1)、受体相互作用蛋白3(RIP3)和混合谱系激酶结构域样蛋白(MLKL)均受到热休克蛋白90的调控。而天然产物Kongensin A (KA)是一种热休克蛋白90抑制剂,热休克蛋白90受到抑制后进而阻断了坏死性凋亡途径。进一步研究坏死性凋亡途径及其对慢性肾脏病的影响,必将为慢性肾脏病的防治提供新的靶点。

Necroptosis plays a vital role in the pathogenesis of inflammatory,immune,and neurodegenerative diseases.The studies have shown that necroptosis is involved in the development of chronic kidney disease (CKD),but the precise molecular mechanism has not been fully elucidated.As an important component of molecular chaperone,heat shock protein 90 (HSP90)has a variety of substrate proteins and is widely involved in many vital activities,which is indispensable to maintain the homeostasis of proteins within cells.With the continuing pursuit of the research,the researchers have found that the core component of necroptosis's pathway,such as receptor interacting protein 1 (RIP1),receptor interacting protein 3 (RIP3)and mixed lineage kinase domain like pseudokinase (MLKL),were regulated by HSP90. Moreover,the natural product Kongensin A (KA)is a HSP90 inhibitor,which can inhibit HSP90 and thus block the necrotic apoptotic pathway.The further research on the pathway of necroptosis and its influence on CKD will provide new biological targets for the prevention and treatment of CKD.