Chemoproteomics identifies Ykt6 as the direct target of schisandrin A for neuroprotection  

作　　者：Tiantian Wang Yu Zhou Hao Zheng Tao Shen Dongmei Wang Jinlan Zhang 

机构地区：[1]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

出　　处：《Chinese Chemical Letters》2023年第6期401-405,共5页中国化学快报（英文版）

基　　金：supported by the CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2021-I2M-1-069,2022-12M-2-002);Beijing Municipal Natural Science Foundation,China(No.7222259)。

摘　　要：Schisandrin A is a natural dibenzocyclooctene lignan with potent neuroprotective activity.However,the specific mechanisms or direct target proteins have not been clarified up to now.In this study,we designed and synthesized the probes of schisandrin A with photoreactive diazirine and clickable alkyne to identify its direct target in SH-SY5Y cells by employing activity-based protein profiling(ABPP)technique.Ykt6 was prominent among the 13 proteins obtained with high confidence and we confirmed Ykt6 as the direct target of schisandrin A by CETSA,IF,SPR and knockdown assay.Functionally,schisandrin A protected the cells against the injury induced by glutamate by regulating autophagy via Ykt6.This discovery may provide a novel therapeutic option for various neuronal cell damage-mediated diseases.

关 键 词：Schisandrin A Activity-based protein profiling(ABPP) NEUROPROTECTION Ykt6 AUTOPHAGY 

分 类 号：R285[医药卫生—中药学]