Fig. 7. Conceptual model demonstrating rational for how small molecules like ZYA could be useful to stimulate degradation of metastable proteins associated with neurodegenerative disease, and perhaps could even circumvent inhibition by some pathological oligomers.

Small molecules that function similar to ZYA, have the potential to function at two different beneficial stages of protein degradation: (1) to upregulate the degradation of unstructured proteins that could misfold, oligomerize, aggregate, and become toxic, and (2) to restore normal proteasome function to proteasomes that could be impaired by toxic oligomers.