β-分泌酶抑制剂的筛选方法及其天然来源的研究进展

Review on the Screening Methods and Natural Sources of β-Secretase Inhibitors

β-淀粉样蛋白(Aβ)的聚集是目前公认的导致阿尔茨海默病(AD)发病的关键因素,而β-分泌酶(BACE1)是将大脑中的淀粉样β-蛋白前体(APP)转化成Aβ的第一个蛋白酶,也是Aβ产生的限速酶。因此,对BACE1的抑制是有效治疗AD的策略之一。本文阐述了目前可用于β-分泌酶抑制剂筛选的荧光法、可见光比色法和酵母细胞筛选模型的原理和特点,并对来源于植物、微生物、动物的天然β-分泌酶抑制剂的研究进展进行了综述,为更多活性更强、毒副作用更小的抗AD天然产物先导化合物的发现和结构优化提供了借鉴和启示。

The aggregation of amyloid β-protein is widely recognized as the key factor leading to Alzheimer＇s disease （AD）, while β-secretase（ BACE1 ） is the enzyme that initiates the production of Aft by cleaving the extracellular domain of amyioid β-protein precursor（APP） and meanwhile the rate-limiting enzyme. Thus ,inhibitors of BACE1 are being considered to be one of the effective strategies in the treatment of AD. This article describes the principle and characteristics of current screening models for the β-secretase inhibitors, including fluorescence, visible colorimetry, and the yeast cell screening models. In addition, the natural β-secretase inhibitors which come from plants, microorganisms and animals, were also reviewed. Thereby,it provided reference and inspiration on the finding and structural optimization of anti-AD natural product lead compounds with higher activity and lower toxic side effects.