Novel potential target pathway to help prevent Alzheimer's dementia

Researchers at Washington University School of Medicine found a way to increase clearance of waste products from the brains of mice by ramping up a genetic quirk known as readthrough. This same strategy also may be effective for other neurodegenerative diseases characterized by the buildup of toxic proteins, such as Parkinson's disease, the researchers said.

The researchers created tools to see whether the long form of aquaporin 4 behaved differently in the brain than the regular form. They found the long form- but not the short one-in the so-called endfeet of astrocytes. Astrocytes are a kind of support cell that help maintain the barrier between the brain and the rest of the body. Their end feet wrap around tiny blood vessels in the brain and help regulate blood flow. Astrocytic endfeet are the perfect place to be if your job is to keep the brain free of unwanted proteins by flushing waste out of the brain and into the bloodstream, where it can be carried away and disposed of.

Thinking that increasing the amount of long aquaporin 4 might increase waste clearance, the team screened 2,560 compounds for the ability to increase readthrough of the aquaporin 4 gene. He found two: apigenin, a dietary flavone found in chamomile, parsley, onions and other edible plants; and sulphaquinoxaline, a veterinary antibiotic used in the meat and poultry industries.

Both the compounds have limitations for human use however the authors said that, "Just knowing that it's targetable at all by a drug is a helpful hint that there's going to be something out there we can use."

Ref:

Joseph D. Dougherty et al,Aqp4 stop codon readthrough facilitates amyloid-β clearance from the brain,Brain.