Aspirin inhibits proteasomal degradation and promotes α-synuclein aggregate clearance through K63 ubiquitination

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	Aspirin inhibits proteasomal degradation and promotes α-synuclein aggregate clearance through K63 ubiquitination
	Gao, J; Liu, Y; Si, CF; Guo, R; Hou, SQ; Liu, XS; Long, HF; Liu, D; Xu, DC; Zhang, ZR; Liu, C; Shan, B; Turck, CW; He, KW; Zhang, YY
	2025
发表期刊	NAT COMMUN
卷号	16 期号:1
摘要	Aspirin is a potent lysine acetylation inducer, but its impact on lysine ubiquitination and ubiquitination-directed protein degradation is unclear. Herein, we develop the reversed-pulsed-SILAC strategy to systematically profile protein degradome in response to aspirin. By integrating degradome, acetylome, and ubiquitinome analyses, we show that aspirin impairs proteasome activity to inhibit proteasomal degradation, rather than directly suppressing lysine ubiquitination. Interestingly, aspirin increases lysosomal degradation-implicated K63-linked ubiquitination. Accordingly, using the major pathological protein of Parkinson's disease (PD), alpha-synuclein (alpha-syn), as an example of protein aggregates, we find that aspirin is able to reduce alpha-syn in cultured cells, neurons, and PD model mice with rescued locomotor ability. We further reveal that the alpha-syn aggregate clearance induced by aspirin is K63-ubiquitination dependent in both cells and PD mice. These findings suggest two complementary mechanisms by which aspirin regulates the degradation of soluble and insoluble proteins, providing insights into its diverse pharmacological effects that can aid in future drug development efforts.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14730
专题	昆明动物研究所
推荐引用方式 GB/T 7714	Gao, J,Liu, Y,Si, CF,et al. Aspirin inhibits proteasomal degradation and promotes α-synuclein aggregate clearance through K63 ubiquitination[J]. NAT COMMUN,2025,16(1).
APA	Gao, J.,Liu, Y.,Si, CF.,Guo, R.,Hou, SQ.,...&Zhang, YY.(2025).Aspirin inhibits proteasomal degradation and promotes α-synuclein aggregate clearance through K63 ubiquitination.NAT COMMUN,16(1).
MLA	Gao, J,et al."Aspirin inhibits proteasomal degradation and promotes α-synuclein aggregate clearance through K63 ubiquitination".NAT COMMUN 16.1(2025).

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