Journal article

Nucleus distribution of cathepsin B in senescent microglia promotes brain aging through degradation of sirtuins

Jie Meng, Yicong Liu, Zhen Xie, Hong Qing, Peng Lei, Junjun Ni

Neurobiology of Aging | ELSEVIER SCIENCE INC | Published : 2020

Abstract

Cathepsin B (CatB) leakage from the lysosome into the cytosol in senescent microglia is associated with cognitive impairment. However, whether cellular compartmental translocation of CatB is associated with brain aging remains unclear. In the present study, increased CatB was found in the nucleus of CatB-overexpressed microglia followed by L-leucyl-L-leucine methyl ester, a lysosome-destabilizing reagent, and in the nuclear fraction of the cortex and hippocampus from aged mice. Moreover, CatB enzymatic activity examination showed the nuclear CatB exhibited the proteolytic activity to cleave its specific substrates. The amount of sirtuin1 (Sirt1), Sirt6, Sirt7, and p-Sirt1 was decreased in th..

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Grants

Awarded by Ministry of Science and Technology of China


Awarded by National Natural Science Foundation of China


Awarded by Beijing Institute of Technology Research Fund Program for Young Scholars


Awarded by National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University


Awarded by Post Doctor Research Program of West China Hospital, Sichuan University


Funding Acknowledgements

The authors would like to thank Christoph Peters (Albert-Ludwigs-Universitat Freiburg) for providing CatB knock-out mice. This work was supported by the Ministry of Science and Technology of China (2018YFC1312300 to PL and HQ), the National Natural Science Foundation of China (81870844, 81671268 to HQ; 81722016 to PL), Beijing Institute of Technology Research Fund Program for Young Scholars (2020CX04166 to JN), the National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (Z2018B03 to PL), and the Post Doctor Research Program of West China Hospital, Sichuan University (2020HXBH063 to JM). Authors' contributions: JM, HQ, PL, and JN conceived of and raised funds for the study. JM, YL, ZX, HQ, PL, and JN designed and performed the experiments. HQ, PL, and JN supervised the experiments. JM and JN integrated the data and wrote the drafts of the manuscript. All authors edited the manuscript.