Development of small‐molecule based human 20S Proteasome Activators: A novel therapeutic target to combat amyloid plaques in Alzheimer's disease

This study introduces direct proteasome activation via gate-opening as a novel therapeutic approach for neurodegenerative diseases. Validated in SH-SY5Y cells and Alzheimer's mouse models, the findings demonstrate reduced amyloid plaques, improved memory, and enhanced neuroprotection. These results establish a robust foundation for advancing proteasome activators as therapeutic agents.