Harnessing the Protein CHIP/STUB1 to Reduce Alzheimer's Brain Pathology

The goal of this study is to develop and deliver an enhanced, protective CHIP/Stub1 variant to neurons as a means to reduce pathological tau and hence alleviate Alzheimer’s symptoms.

The research focuses on the role of the protein CHIP/STUB1 in Alzheimer’s disease, particularly its ability to prevent the aggregation of tau proteins linked to the disease’s progression. By engineering CHIP variants that enhance its chaperone function, the study aims to reduce tau pathology and improve cognitive function in Alzheimer’s patients. This innovative approach could lead to new gene therapies for Alzheimer’s and other tau-related diseases.

CHIP/Stub1 is a protein that can seek out, target, and detoxify toxic tau aggregates that are hallmarks of Alzheimer’s disease. Understanding how active CHIP variants work will allow us to engineer optimal anti-tau CHIP variants that prevent tau aggregation. These serve as potential gene therapies with far-reaching translational implications.

First, the benefits are conceptual since we will understand of how tau proteins cause disease and how a single protein has the ability to counteract tau’s toxic effects in the brain. Second, the benefits are technical since we are developing new tools, models, and approaches that provide a tangible product that will help build new therapies. Lastly, our study will spur new lines of investigation from others in the field that work on tangentially related genes that may also have anti-tau activity.