胱抑素C和组织蛋白酶B轴对β淀粉样肽聚集和降解的影响

Effect of Human Cystatin C and Cathepsin B-Axis onβ-Amyloid Aggregation and Degradation

淀粉样蛋白沉积疾病是由错误折叠的蛋白在细胞内外聚集而引起的一类蛋白质构象类疾病.淀粉样肽β(Amyloidβ,Aβ)被认为是引起阿尔茨海默病(Alzheimer′s disease,AD)的致病蛋白,Aβ是由淀粉样前体蛋白(Amyloid precursor protein,APP)经一系列分泌酶切割而产生的,由于切割方式不同产生多种不同的肽段类型.人胱抑素C(Human cystatin C,HCC)是一种普遍存在于人体体液和组织液中的半胱氨酸蛋白酶抑制剂.HCC可与可溶性的Aβ结合,它与Aβ的原纤维共定位于AD病人的脑部病灶组织,表明它具有一定的神经保护作用.组织蛋白酶B(Cathepsin B,Cat B)是一种半胱氨酸蛋白酶,主要存在于脑内胶质细胞的溶酶体中.Aβ含量的增加可以刺激胶质细胞释放Cat B,对Aβ浓度进行调节,但Cat B在中枢神经系统中的Aβ前体蛋白处理和Aβ42代谢中发挥的作用仍有待确定.本文阐述了HCC-Cat B轴可能在AD进程的不同阶段发挥了不同的作用的观点,以期为AD的预防和治疗提供有价值的信息.

Amyloid deposition diseases are a type of protein conformational diseases caused by the accumulation of misfolded proteins inside and outside cells.Amyloidβ(Aβ)is considered to be the pathogenic protein of Alzheimer′s disease(AD).Aβis produced by the cleavage of Amyloid precursor protein(APP)by a series of secretases,and there are many different peptides due to different cleavage sits.Human cystatin C(HCC)has been found in all mammalian body fluids and tissues.It can inhibit the activity of cysteine protease extracellularly.HCC′s association with Aβresults in a concentration-dependent inhibition of Aβfibril formation and is considered to have neuroprotective effects.Cathepsin B(Cat B)is a cysteine protease that exists mainly in the lysosomes of glial cells in the brain.Increased Aβcontent can stimulate the release of Cat B by glial cells to regulate Aβ,but its exact role in APP processing and Aβ42 degradation in the central nervous system remains to be determined.This review elaborates that HCC-Cat B axis may play different roles in different stages of AD,hopping to provide valuable information for the prevention and treatment of AD.