Exhaustive exercise decreases tau phosphorylation and modifies biological processes associated with the protein translation and electron transport chain in P301L tau transgenic mice

He，Kaiwu1,2,3; Nie，Lulin1,4; Yang，Chen1; Liu，Zizhen5; Huang，Xinfeng1; Li，Shupeng5; Yang，Xifei1

2024-03-01

10.1016/j.exger.2024.112375

Experimental Gerontology   影响因子和分区

0531-5565

1873-6815

Stress response is a fundamental mechanism for cell survival, providing protection under unfavorable conditions. Mitochondrial stress, in particular, can trigger mitophagy, a process that restores cellular health. Exhaustive exercise (EE) is a form of acute mitochondrial stress. The objective of this current study is to investigate the impact of EE on tau pathology in pR5 mice, as well as the potential underlying mechanisms. To evaluate this, we examined the levels of total and phosphorylated tau in the hippocampus of pR5 mice, both with and without EE treatment. Furthermore, the application of weighted correlation network analysis (WGCNA) was employed to identify protein modules associated with the phenotype following the proteomic experiment. The findings of our study demonstrated a significant decrease in tau phosphorylation levels upon EE treatment, in comparison to the pR5 group. Moreover, the proteomic analysis provided additional insights, revealing that the mitigation of tau pathology was primarily attributed to the modulation of various pathways, such as translation factors and oxidative phosphorylation. Additionally, the analysis of heatmaps revealed a significant impact of EE treatment on the translation process and electron transport chain in pR5 mice. Furthermore, biochemical analysis provided further confirmation that EE treatment effectively modulated the ATP level in pR5 mice. In conclusion, our study suggests that the observed decrease in tau phosphorylation resulting from EE treatment may primarily be attributed to its regulation of the translation process and enhancement of mitochondrial function.

Exhaustive exercise (EE) Mitochondrial stress Proteomics Weighted correlation network analysis (WGCNA)

SCI

英语

其他

CLINICAL MEDICINE

2-s2.0-85184756094

Scopus

1.Key Laboratory of Modern Toxicology of Shenzhen,Shenzhen Medical Key Discipline of Health Toxicology (2020–2024),Shenzhen Center for Disease Control and Prevention,Shenzhen,518055,China
2.Department of Anesthesiology,Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,No. 1017, Dongmen North Road,518020,China
3.Integrated Chinese and Western Medicine Postdoctoral Research Station,Jinan University,Guangzhou,China
4.Institute of New Drug Research,International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education,Jinan University College of Pharmacy,Jinan University,Guangzhou,China
5.School of Chemical Biology and Biotechnology,Peking University Shenzhen Graduate School,Shenzhen,518055,China

He，Kaiwu,Nie，Lulin,Yang，Chen,et al. Exhaustive exercise decreases tau phosphorylation and modifies biological processes associated with the protein translation and electron transport chain in P301L tau transgenic mice[J]. Experimental Gerontology,2024,187.

He，Kaiwu.,Nie，Lulin.,Yang，Chen.,Liu，Zizhen.,Huang，Xinfeng.,...&Yang，Xifei.(2024).Exhaustive exercise decreases tau phosphorylation and modifies biological processes associated with the protein translation and electron transport chain in P301L tau transgenic mice.Experimental Gerontology,187.

He，Kaiwu,et al."Exhaustive exercise decreases tau phosphorylation and modifies biological processes associated with the protein translation and electron transport chain in P301L tau transgenic mice".Experimental Gerontology 187(2024).