Washington University School of Medicine researchers have uncovered an entirely new druggable pathway with the potential for revolutionary treatment and/or prevention of Alzheimer’s dementia. Using mice as test subjects, the researchers devised a means of increasing systemic clearance of waste products via exploitation of readthrough, a genetic quirk wherein the brain protein aquaporin 4 is synthesized with a seemingly superfluous bit of tail on the end. At first glance, this tail was thought to be nothing more than a quality control glitch in the protein manufacturing process.
“Sometimes the protein-synthesizing machinery blew right through the stop sign at the end and made this extra bit on the end of aquaporin 4,” said the study’s senior author and a Washington University professor of genetics and psychiatry, Dr. Joseph D. Dougherty. “At first, we thought it couldn’t possibly be relevant. But then we looked at the gene sequence, and it was conserved across species. And it had this really striking pattern in the brain: It was only in structures that are important for waste clearance. So that’s when we got excited.”
Already known was the fact that the cell’s protein-building machinery sometimes continues on past its expected stopping point. This phenomenon, the aforementioned readthrough that is the crux of this discovery, generates extended proteins with different functionalities than regular forms. The new research could prove effective in dealing with other toxic protein-caused neurodegenerative diseases, including Parkinson’s disease.