Novel compound clears harmful protein, protects neurons in frontotemporal dementia models

New research from Washington University School of Medicine in St. Louis adds to growing evidence that helping brain cells break down and eliminate their own cellular waste is a promising treatment strategy for a variety of neurodegenerative diseases. In lab experiments, the researchers found that exposure to a novel compound can clear a harmful protein from human neurons modeling frontotemporal dementia - a devastating and ultimately fatal condition - and prevent those neurons from dying.

According to the researchers, the study's results provide further evidence that enhancing autophagy, a key cellular process involved in breaking down and recycling cellular waste, could help treat neurodegenerative diseases. Autophagy is known to decline with age, so strategies to restore it could help address multiple age-related diseases.

The researchers, led by Celeste Karch, PhD, the Barbara Burton and Reuben M. Morriss III Professor in the WashU Medicine Department of Psychiatry, studied a specific mutation in a brain protein called tau that causes the protein to become misfolded and alter its normal function. In general, when tau proteins become misfolded, they build up inside neurons and contribute to various forms of dementia, including Alzheimer's dementia and frontotemporal dementia, a neurodegenerative disease similar to Alzheimer's that often strikes earlier - in middle age - and typically involves significant changes in personality and behavior that precede cognitive decline.

We found that this tau mutation can clog the cell's normal cellular clean-up system and interfere with how cells in the brain clean up misfolded proteins. One compound in particular had an impressive effect in making the cells look almost normal in their clearance of misfolded proteins. In the future, we can envision new therapies for neurodegenerative diseases that may be similar to what we have now for cancer: multi-pronged treatments that combine several drugs attacking different aspects of the disease simultaneously."