The Dynamic SUMOylation Changes and Their Potential Role in the Senescence of APOE4 Mice

Yangqi Xu; Wenwen Cai; Shaoming Sang; Xiaoqin Cheng; Boru Jin; Xiangteng Zhao; Chunjiu Zhong

doi:10.3390/biomedicines12010016

The Dynamic SUMOylation Changes and Their Potential Role in the Senescence of APOE4 Mice

Biomedicines. 2023 Dec 20;12(1):16. doi: 10.3390/biomedicines12010016.

Authors

Yangqi Xu¹, Wenwen Cai¹, Shaoming Sang¹, Xiaoqin Cheng¹, Boru Jin¹, Xiangteng Zhao^{1

2}, Chunjiu Zhong¹

Affiliations

¹ Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
² Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Abstract

The ε4 allele of apolipoprotein E (APOE4) and aging are the major risk factors for Alzheimer's disease (AD). SUMOylation is intimately linked to the development of AD and the aging process. However, the SUMOylation status in APOE4 mice has not been uncovered. In this study, we investigated SENP1 and SUMOylation changes in the brains of aged APOE3 and APOE4 mice, aiming to understand their potential impact on mitochondrial metabolism and their contribution to cellular senescence in APOE4 mice. Concurrently, SUMO1-conjugated protein levels decreased, while SUMO2/3-conjugated protein levels increased relatively with the aging of APOE4 mice. This suggests that the equilibrium between the SUMOylation and deSUMOylation processes may be associated with senescence and longevity. Our findings highlight the significant roles of SENP1 and SUMOylation changes in APOE4-driven pathology and the aging process.

Keywords: APOE4; Alzheimer’s disease; SENP; SUMOylation; aging.

Abstract

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