Stimulating Proteasome Activity for the Treatment of Alzheimer’s Disease (Year 1)

Alzheimer’s disease—caused by the accumulation of toxic proteins that impair cell function and lead to neuronal death—poses a major unmet health need, since neither cures nor treatments that address the root cause of the disease exist. All cells have the capacity to clear out and degrade unwanted and potentially dangerous protein buildup. Unfortunately, this “trash removal” process becomes less efficient with age. The lab recently discovered a novel mechanism that stimulates the activity of “proteasomes,” the nano-machines responsible for the removal of unwanted proteins. We have found this mechanism is essential for the maintenance of neuronal health and brain function. Mutations in this pathway are found in human patients suffering from age-related neurological diseases. Stimulating the activity of this protein clearance pathway can prevent neuronal degeneration and extend life span in animal models. We identified an inhibitor of this pathway that represents a promising drug target for the treatment of Alzheimer’s disease. This research has the potential to radically transform the field and yield a novel class of drugs that promote clearance of toxic proteins.