Stimulating Synaptic Proteasome Activity for the Treatment of Alzheimer’s Disease

2021, 2022

Alzheimer’s disease (AD) poses a major unmet health need since neither cures nor treatments that address its root cause currently exist. AD is caused by the accumulation of toxic proteins that impair cell function and eventually lead to the death of nerve cells. All our cells have potent clearance mechanisms to degrade unwanted and potentially dangerous proteins. Unfortunately, this “trash removal” process becomes less efficient with age.

We recently discovered a novel mechanism that transports “proteasomes,” the nano-machines responsible for the removal of unwanted proteins, to nerve endings, and showed that this mechanism is essential for neuronal health and brain function. Moreover, this process becomes less efficient with age; mutations in this pathway are found in human patients suffering from age-related neurological diseases, including AD. Importantly, stimulating the activity of this protein clearance pathway can prevent neuronal degeneration and extend lifespan in animal models. Finally, we identified an inhibitor of this pathway that represents a promising drug target for the treatment of AD. This work has the potential to radically transform the field and yield a novel class of drugs that promotes clearance of toxic proteins and stimulates brain function in AD.


Funding to Date



Drug Discovery, Drug Screening Projects


Hermann Steller, Ph.D.