UCHL1 and Alzheimer disease: However, the exact mechanism by which exercise regulates the expression of E3 ligases (CHIP, UCHL-1) to affect UPS function is not clear in the AD state, which was why this study was conducted in APP/PS1 mice to find out whether exercise could improve the pathological phenotype of AD by affecting the PI3K/Akt pathway and thus altering the expression of E3 ubiquitin ligase.