RESUMO
γ-Secretase is aⅠtransmembrane protease associated with Alzheimer disease(AD), and including four subunits:presenilin,presenilin enhancer-2,anterior-pharynx-defective1 and nicastrin. In recent studies,the ultra-high-resolution cryo-electron microscope has been used for the first time, revealing the humanγ-secretase″horseshoe″,the three-dimensional structure and the arrangement of the subunits. This technique has shed light on the regulation of the enzyme pathway and mechanism. In addition,the γ-secretase modulators,including non-steroidal anti-inflammatory drugs,have been shown in vitro to inhibit γ-secretase activity and selectively reduce the level of Aβ42 against AD. They have provided an effective approach,with broad prospects for development. Studies in this area have become a hot topic in recent years. Here we summarized the γ-secretase subunits regulatory pathways, humanγ-secretase fine three-dimensional structure andγ-secretase modulators .
