Abstract: 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 Aβ by cleaving the extracellular domain of amyloid 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.

Key words: amyloid &beta, -protein, alzheimer&prime, s disease, &beta, -secretase inhibitors, natural products