Citation: Tiantian Wang, Yu Zhou, Hao Zheng, Tao Shen, Dongmei Wang, Jinlan Zhang. Chemoproteomics identifies Ykt6 as the direct target of schisandrin A for neuroprotection[J]. Chinese Chemical Letters, ;2023, 34(6): 107887. doi: 10.1016/j.cclet.2022.107887 shu

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

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

wangdmchina@imm.ac.cn

zhjl@imm.ac.cn

Received Date: 2 August 2022
Revised Date: 2 October 2022
Accepted Date: 4 October 2022
Available Online: 9 October 2022

Figures(4)

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.
- Schisandrin A,
- Activity-based protein profiling (ABPP),
- Neuroprotection,
- Ykt6,
- Autophagy
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