Researchers have found a way to increase the clearance of waste products from the brains of mice by ramping up a genetic quirk known as readthrough.A new druggable pathway that potentially could be used to help preventdementia has been discovered by researchers at Washington University School of Medicine in St. Louis.
An extended form of the protein aquaporin 4 lines the edges of tiny blood vessels in the brain. Cell nuclei are visible in blue. Researchers at Washington University School of Medicine in St. Louis have found a new druggable pathway that enhances the amount of long aquaporin 4 near blood vessels and increases the clearance of waste from the brain. The findings potentially could lead to new therapies to prevent Alzheimer’s dementia.
Sapkota and Dougherty created special tools to see whether the long form of aquaporin 4 behaved differently in the brain than the regular form. They discovered 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 endfeet wrap around tiny blood vessels in the brain and help regulate blood flow.
The scientists studied mice that were genetically engineered to have high levels of amyloid in their brains. They treated the mice with apigenin; sulphaquinoxaline; an inert liquid; or a placebo compound that has no effect on readthrough. Mice treated with either apigenin or sulphaquinoxaline cleared amyloid beta significantly faster than those treated with either of the two inactive substances.