Figure 8.

Hypothesis of NH037 and daidzein targeting UPS function in SCA3-iPSC-derived neurons. In SCA3-iPSC-derived neurons, UPS function is impaired under environmental stress (such as MG132 exposure), and ubiquitinated proteins and polyQ-expanded ATXN3 protein are accumulated in cells. The resulting abnormal aggregation increased the production of oxidative stress and cytotoxicity. NH037 and daidzein promote protein degradation to reduce oxidative stress and cytotoxicity by improving proteasome activity in SCA3-iPSC-derived neurons.